Government Regulation

Regulation by government authorities in the United States and other countries is a significant factor in the production and marketing of our products and our ongoing R&D activities. To clinically test, manufacture and market products for therapeutic use, we must satisfy mandatory procedures and safety and effectiveness standards established by various regulatory bodies. Compliance with these standards is complex, and failure to comply with any of these standards can result in significant implications. See Item 1A. Risk Factors for a discussion of factors, including global regulatory implications, that can adversely impact our development and marketing of commercial products.

Regulation in the United States

In the United States, the Public Health Service Act; the ~~Federal Food, Drug, and Cosmetic Act (FDCA);~~FDCA; and the regulations promulgated thereunder as well as other federal and state statutes and regulations govern, among other things, the production, research, development, testing, manufacture, quality control, labeling, storage, record keeping, approval, advertising, promotion and distribution of our products in addition to the reporting of certain payments and other transfers of value to healthcare professionals and teaching hospitals.

Clinical Development and Product Approval. Drug development in our industry is complex, challenging and risky, and failure rates are high. Product development cycles are typically very long—approximately 10 to 15 years from discovery to market. A potential new medicine must undergo many years of preclinical and clinical testing to establish its safety and efficacy for use in humans at appropriate dosing levels and with an acceptable risk–benefit profile. We continue to work toward reducing cycle times by applying our expertise in human genetics and innovation in technology, clinical trials and real-world evidence.

After laboratory analysis and preclinical testing in animals, we file an ~~Investigational New Drug Application (IND)~~IND with the FDA to begin human testing. Typically, we undertake an FDA-designated three-phase human clinical testing program.

•In phase 1, we conduct small clinical trials to investigate the safety and proper dose ranges of our product candidates in a small number of human subjects.

•In phase 2, we conduct clinical trials to investigate side-effect profiles and the efficacy of our product candidates in a patient population larger than phase 1 but still relatively small, who have the disease or condition under study.

•In phase 3, we conduct clinical trials to investigate the short- and long-term safety and efficacy of our product candidates, compared to commonly used treatments, in a large number of patients who have the disease or condition under study.

The FDA monitors the progress of each trial conducted under an IND and may, at its discretion, reevaluate, alter, suspend or terminate the testing based on ~~the~~ data accumulated to that point and the FDA’s risk–benefit assessment with regard to the patients enrolled in the trial. The results of preclinical and clinical trials are submitted to the FDA in the form of either a Biologics License Application for biologic products or a ~~NDA~~New Drug Application for small molecule products. We are not permitted to market or promote a new product until the FDA has approved our marketing application.

Approval of Biosimilars. The Affordable Care Act ~~(ACA)~~ authorized the FDA to approve biosimilars via a separate, abbreviated pathway. The pathway allows sponsors of a biosimilar to seek and obtain regulatory approval based in part on the nonclinical-trial and clinical-trial data of an originator product to which the biosimilar has been demonstrated to be “highly similar” and to have no clinically meaningful differences ~~in terms of~~with regard to safety, purity and potency. The relevance of demonstrating “similarity” is that in many cases, biosimilars can be brought to market without conducting the full suite of clinical trials typically required of originators, because risk–benefit has previously been established. To preserve incentives for future innovation, the law establishes a period of exclusivity for originators’ products, which in general prohibits biosimilars from gaining FDA approval based in part on reliance on or reference to the originator’s data in their application to the FDA for 12 years after initial FDA approval of the originator product. The law does not change the duration of patents granted on biologic products. As part of the implementation of the abbreviated approval pathway for biosimilars, the FDA released a number of guidance documents, some of which remain in draft form. See Item 1A. Risk Factors—We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future.

Regulation of Product Marketing and Promotion. The FDA regulates the marketing and promotion of drug products. Our product promotions for approved product indications must comply with the statutory standards of the FDCA and the FDA’s implemented regulations and guidance. The FDA’s review of marketing and promotional activities encompasses but is not limited to direct-to-consumer advertising, healthcare-provider-directed advertising and promotion, sales representative communications to healthcare professionals, promotional programming and promotional activities involving electronic media. The FDA may also review industry-sponsored scientific and educational activities that make representations regarding product safety or efficacy in a promotional context. The FDA may take enforcement action against a company for promoting unapproved uses of a product or for other violations of the FDA’s advertising and labeling laws and regulations. Enforcement action may include product seizures, injunctions, civil or criminal penalties or regulatory letters, which may require corrective advertising or other corrective communications to healthcare professionals. Failure to comply with the FDA’s regulations also can result in adverse publicity or increased scrutiny of company activities by the U.S. Congress or other legislators. Additionally, as described below, such failure may lead to additional liability under U.S. healthcare fraud and abuse laws.

Regulation of Manufacturing Standards. The FDA regulates and inspects the equipment, facilities, laboratories and processes used in the manufacturing and testing of products prior to granting approval to market products. If after receiving approval from the FDA we make a material change in manufacturing equipment, location or process, additional regulatory review may be required. We also must adhere to current Good Manufacturing Practice regulations and product-specific regulations enforced by the FDA through its facilities inspection program. The FDA conducts regular, periodic visits to reinspect our equipment, facilities, laboratories and processes following an initial approval.

Regulation of Combination Products. Combination products are defined by the FDA as products composed of two or more regulated components (e.g., a biologic and/or drug and a device). Biologics/drugs and devices each have their own regulatory requirements, and combination products may have additional requirements. A number of our marketed products meet this definition and are regulated under this framework, and we expect that a number of our pipeline product candidates will be evaluated for regulatory approval under this framework as well.

Regulation outside the United States

In ~~European Union (EU)~~EU countries as well as in the United Kingdom, Switzerland, Canada, Australia and Japan, regulatory requirements and approval processes are similar in principle to those in the United States.

In the EU, there are currently two potential tracks for seeking marketing approval for a product not authorized in any EU member state: a decentralized procedure and a centralized procedure. In the decentralized procedure, identical applications for marketing authorization are submitted simultaneously to the national regulatory agencies. Regulatory review is led by one member state (the reference-member state), and its assessment—based on safety, quality and efficacy—is reviewed and approved (assuming there are no concerns that the product poses a serious risk to public health) by the other member states from which the applicant is seeking approval (the concerned-member states). The decentralized procedure leads to a series of single national approvals in all relevant countries. In the centralized procedure, which is required of all products derived from biotechnology, a company submits a single ~~MAA~~Marketing Authorisation Application to the EMA, which conducts an evaluation of the dossier, drawing upon its scientific resources across Europe. If the drug product is proven to fulfill requirements for quality, safety and efficacy, the EMA’s ~~Committee for Medicinal Products of Human Use (CHMP)~~CHMP adopts a positive opinion, which is transmitted to the ~~European Commission (EC)~~EC for final decision on granting of the marketing authorization. Even though the EC generally follows the CHMP’s opinion, it is not bound to do so. Subsequent commercialization is enabled by country-by-country reimbursement approval.

In the EU, biosimilars are approved under a specialized pathway of the centralized procedure. As with the U.S. pathway, an applicant seeks and obtains regulatory approval for a biosimilar once the data exclusivity period for the original reference product has expired, relying in part on the data submitted for the originator product together with data evidencing that the biosimilar is “highly similar” ~~in terms of~~with regard to quality, safety and efficacy to the original reference product authorized in the European Economic Area.

~~As a result of the United Kingdom’s decision~~ See Item 1A. Risk Factors—We currently face competition from biosimilars and generics and expect to ~~leave the EU, the EMA in March 2019 relocated to Amsterdam. The United Kingdom officially left the EU in January 2020,~~face increasing competition from biosimilars and in December 2020, a new trade deal was agreed that starts to clarify how U.K. medicines will be independently supervised and where continued collaborations and recognitions can be expected. Amgen continues to monitor future negotiations to ensure no interruptiongenerics in the ~~supervision, regulation or supply of medicines in the United Kingdom and Europe.~~future.

Other countries such as ~~Russia, Turkey and~~ those in Latin America and the Middle East have review processes and data requirements similar to those of the EU and in some cases can rely on prior marketing approval from U.S. or EU regulatory authorities. The regulatory process in these countries may include manufacturing/testing facility inspections, testing of drug product upon importation and other domestic requirements.

In Asia Pacific, a number of countries such as China, Japan, South Korea and Taiwan may require local clinical-trial data for bridging purposes as part of the drug registration process in addition to global clinical trials, which can add to overall drug development and registration timelines. In most of the Asian markets, registration timelines depend on marketing approval in the United States or the EU. In some markets in Asia, such as China, Indonesia and Thailand, ~~the~~ regulatory timelines can be less predictable. The regulatory process may also include manufacturing/testing facility inspections, testing of drug product upon importation and other domestic requirements. Countries such as Australia and Japan have more-mature systems that would allow for submissions under more-competitive time frames. ~~Regarding~~With regard to biosimilars, several of these countries have pathways to register biosimilars (e.g., Australia, India, Singapore, South Korea and Taiwan), and biosimilar products are already present on the markets (e.g., Australia and South Korea).

In some countries, such as Japan and those in the EU, medical devices may be subject to regulatory regimes whereby manufacturers must establish that their medical devices conform to essential requirements set out in the law for the particular device category. For example, in the EU, with limited exceptions, medical devices placed on the market must bear the Conformité Européenne marking to indicate their conformity with legal requirements.

Postapproval Phase

After approval, we continue to monitor adverse events and product complaints reported following the use of our products through routine postmarketing surveillance and studies when applicable. We report such events to the appropriate regulatory agencies as required by local regulations for individual cases and aggregate reports. We proactively monitor (according to good pharmacovigilance practices) and ensure the implementation of signal detection, assessment and the communication of adverse events that may be associated with the use of our products. We also proactively monitor product complaints through our quality systems, which includes assessing our drug delivery devices for device complaints, adverse events and malfunctions. We may also be required by regulatory agencies to conduct further clinical trials on our marketed products as a condition of their approval or to provide additional information on safety and efficacy. Health regulators, including the FDA, have authority to mandate labeling changes to products at any point in a product’s life cycle based on new safety information or as part of an evolving label change to a particular class of products.

Health regulators, including the FDA, also have authority both before orand after approval to require that a company to implement a risk management program for a product to ensure that the benefits of the drug outweigh the risks. Each risk management program is unique and varies depending on the specific factors required. In the United States, such a risk management program is known as a ~~risk evaluation and mitigation strategy (REMS),~~REMS, and we currently have REMSs for Prolia,®, Nplate® and ~~BLINCYTO~~®.BLINCYTO.

Other Regulation

We are also subject to various laws pertaining to healthcare fraud and abuse, including antikickback laws and false-claims laws. Antikickback laws make it illegal to solicit, offer, receive or pay any remuneration in exchange for or to induce the referral of business, including the purchase or prescribing of a particular drug that is reimbursed by a state or federal program. False-claims laws prohibit knowingly and willingly presenting or causing to be presented for payment to third-party payers (including Medicare and Medicaid) any claims for reimbursed drugs or services that are false or fraudulent, claims for items or services not provided as claimed or claims for medically unnecessary items or services. Violations of fraud and abuse laws may be punishable by criminal and/or civil sanctions, including fines and civil monetary penalties, as well as by the possibility of exclusion from federal healthcare programs (including Medicare and Medicaid). Liability under ~~the~~ false-claims laws may also arise when a violation of certain laws or regulations related to the underlying product (e.g., ~~violations~~a violation regarding improper promotional activity or unlawful payments) contributes to the submission of a false claim.

In 2012, Amgen entered into a corporate integrity agreement with the Office of Inspector General (OIG) of the U.S. Department of Health & Human Services (HHS), which was formally closed out in August 2018. On April 25, 2019, we entered into a settlement agreement with the ~~U.S. Department of Justice (DOJ)~~DOJ and the OIG of the HHS to settle certain allegations related to our support of independent charitable organizations that provide patients with financial assistance to access ~~their~~ medicines. Additionally, we entered into a corporate integrity agreement that requires us to both maintain a corporate compliance program and to undertake a set of defined corporate integrity obligations for a period of five years. Due to the breadth of the statutory provisions and the absence of guidance in the form of regulations or court decisions addressing some of our practices, it is possible that in the future, our practices might be further challenged under antikickback or similar laws.

The ~~U.S. Foreign Corrupt Practices Act (FCPA)~~FCPA prohibits U.S. corporations and their representatives from offering, promising, authorizing or making payments to any foreign government official, government staff member, political party or political candidate in an attempt to obtain or retain business abroad. The scope of the FCPA arguably includes interactions with certain healthcare professionals in many countries. Other countries have enacted similar anticorruption laws and/or regulations. Failure by our employees, agents, contractors, vendors, licensees, partners or collaborators to comply with the FCPA and other anticorruption laws and/or regulations could result in significant civil or criminal penalties.

We are subject to various laws and regulations globally ~~regarding~~with regard to privacy and data protection. These laws and regulations involve the collection, storage, handling, use, disclosure, transfer and security of personal data. The legislative and regulatory environments regarding privacy and data protection are continually evolving and developing asbecause these issues are ~~the~~ subjects of increasing amounts of attention in countries globally. For example, we are subject to the EU’s ~~General Data Protection Regulation (GDPR),~~GDPR, which became effective on May 25, ~~2018, and~~2018; the ~~California Consumer Privacy Act of 2018,~~CCPA, which became effective on January 1, ~~2020.~~2020; the California Privacy Rights Act of 2020, which amended the CCPA and became effective on January 1, 2023; and China’s Personal Information Protection Law, which became effective on November 1, 2021. Other jurisdictions where we operate have enacted or proposed similar legislation and/or regulations.For example, Virginia, Colorado, Utah and Connecticut have all subsequently passed similar consumer privacy laws, which went into effect in Virginia as of January 1, 2023, and will go into effect in Colorado, Utah and Connecticut later in 2023. Failure to comply with these laws could result in significant penalties.

Our business has been and will continue to be subject to various other U.S. and foreign laws, rules and ~~regulations.~~regulations, including provisions of the IRA. See Reimbursement section above.

Research and Development and Selected Product Candidates

We focus our R&D on novel human therapeutics for the treatment of serious illness. We capitalize on our strengths in human genetics, novel biology and protein engineering. We leverage our biologic expertise and ~~take~~seek to choose the optimal modality for a ~~modality-independent approach to R&D.~~drug target and disease. And we use cutting-edge science and technology to study subtle biological mechanisms in search of therapies that will improve the lives of those who suffer from diseases.

Our discovery research programs may therefore yield targets that lead to the development of human therapeutics delivered as large molecules, small molecules, other combination modalities or new modalities. We have reshaped our portfolio and have increasingly focused our efforts on human genetics when possible to enhance the likelihood of success.

~~In response~~Since early 2021, efforts have been under way to control the COVID-19 pandemic. However, uncertainty remains as to the ~~COVID-19~~efficacy of these activities with respect to the ongoing trajectory of the pandemic. Challenges to vaccination efforts, new variants and other causes of virus spread may require governments to change restrictions and/or shutdown requirements in various geographies. As a result, we expect to see continued volatility for at least the duration of the pandemic ~~we managed~~as governments respond to current local conditions. With regard to our clinical ~~development~~trial activities, we are continuously monitoring COVID-19 infection rates, including changes from new variants; we are working to mitigate effects on ~~a case-by-case basis. Patients who were already enrolled~~future study enrollment in ~~studies continued to receive study drug, including through direct-to-patient shipments. For studies that had~~our clinical trials; and we are evaluating the ~~potential for significant benefit~~impact in a serious or life-threatening condition and when site resources enabled new patients to be enrolled safely and monitored closely, we continued enrollment. For clinical trials experiencing uncertainty with regard to the trial sites’ ability to ensure subject safety or data integrity at that time, we temporarily paused enrollment.all relevant countries. We remain focused on supporting our active clinical sites in their providing care for ~~these~~ patients and in our providing investigational drug supply. To date, the majority of clinical trials that were paused at the onset of the pandemic to ensure subject safety or data integrity have resumed. Study enrollments were affected the most in the second quarter of 2020 and by the end of the year resumed to prepandemic levels, although COVID-19 infection rates and related vaccination activities may impact future patient enrollment. We continuously monitor and reevaluate the status of studies, pausing when uncertainty arises with regard to the trial sites’ ability to ensure safety or data integrity. We remain focused on supporting our active clinical sites in providing care for these patients and in providing investigational drug supply. In addition, our R&D organization is supporting efforts to combat the COVID-19 pandemic in a number of ways, including by (i) working to support production of therapeutic antibodies that could diminish the impact of COVID-19 on patients, (ii) joining a public–private partnership between leading companies in our industry and U.S. government health agencies to develop a strategy for a coordinated research response and (iii) participating in platform studies to investigate treatments in adult patients hospitalized with severe COVID-19 infections.

For the years ended December 31, ~~2020, 2019~~2022, 2021 and ~~2018,~~2020, our R&D expenses were ~~$4.2~~$4.4 billion, ~~$4.1~~$4.8 billion and ~~$3.7~~$4.2 billion, respectively.

We have major R&D centers in Thousand Oaks and San Francisco, California; Iceland; and the United Kingdom, as well as smaller research centers and development facilities globally. See Item 2. Properties.

Our clinical trial activities are conducted by both our internal staff and third-party contract clinical trial service providers. To increase the number and diversity of patients available for enrollment in our clinical trials, we have opened clinical sites and will continue opening clinical sites and enrolling patients in a number of geographic locations. See Government Regulation—Regulation in the United States—Clinical Development and Product Approval for a discussion of government regulation over clinical development. Also see Item 1A. Risk Factors—We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications.

Some of our competitors are actively engaged in R&D in areas in which we have products or in which we are developing product candidates or new indications for existing products. For example, we compete with other clinical trials for eligible patients, which may limit the number of available patients who meet the criteria for certain clinical trials. The competitive marketplace for our product candidates is greatly dependent on the timing of entry into the market. Early entry may have important advantages in gaining product acceptance, thereby contributing to a product’s eventual success and profitability. Accordingly, we expect that in some cases, the relative speed with which we can develop products, complete clinical testing, receive regulatory approval and supply commercial quantities of a product to the market will be important to our competitive position.

In addition to product candidates and marketed products generated from our internal R&D efforts, we acquire companies, acquire and license certain product and R&D technology rights and establish R&D arrangements with third parties to enhance our strategic position within our industry by strengthening and diversifying our R&D capabilities, product pipeline and marketed product base. In pursuing these R&D arrangements and licensing or acquisition activities, we face competition from other pharmaceutical and biotechnology companies that also seek to license or acquire technologies, product candidates or marketed products from those entities performing the R&D.

1716

The following table shows a selection of certain of our product candidates by phase of development in our therapeutic areas of focus as of ~~February 2, 2021,~~January 31, 2023, unless otherwise indicated. Additional product candidate information can be found on our website at www.amgen.com. (The website address is not intended to function as a hyperlink, and the information contained on our website is not intended to be a part of this filing.) The information in this section does not include other, nonregistrational clinical trials that we may conduct for purposes other than for submission to regulatory agencies for their approval of a new product indication.

We may conduct nonregistrational clinical trials for various reasons, including to evaluate real-world outcomes or to collect additional safety information with regard to the use of ~~our~~ products.

1817


Molecule		~~Disease/condition~~Investigational indication
Phase 3 programs
AMJEVITA		Interchangeability
Bemarituzumab		GEJ adenocarcinoma
BLINCYTO		Ph-negative B-cell precursor acute lymphoblastic leukemia
EVENITY®		Male osteoporosis
KYPROLIS®		Weekly dosing for relapsed multiple myeloma
LUMAKRAS/LUMYKRAS		Advanced colorectal cancer
Nplate®		Chemotherapy-induced thrombocytopenia
~~Otezla~~Olpasiran®		~~COVID-19~~
	~~Genital psoriasis~~
	~~Mild-to-moderate psoriasis~~
~~Repatha~~®		Cardiovascular disease
~~RIABNI~~OtezlaTM		~~Rheumatoid arthritis~~Genital psoriasis; Palmoplantar pustulosis
~~Sotorasib~~		~~NSCLC with~~ ~~KRAS G12C~~ ~~mutations~~
~~Tezepelumab~~Repatha		Cardiovascular disease
Rocatinlimab		Atopic dermatitis
TEZSPIRE		Chronic rhinosinusitis with nasal polyps; Eosinophilic esophagitis; Severe asthma
ABP 654		~~Psoriasis, psoriatic arthritis and Crohn’s disease~~Investigational biosimilar to STELARA (ustekinumab)
ABP 938		~~Neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy~~Investigational biosimilar to EYLEA (aflibercept)
ABP 959		~~Paroxysmal nocturnal hemoglobinuria (PNH)~~Investigational biosimilar to SOLIRIS (eculizumab)

Phase 2 programs
~~Olpasiran (formerly AMG 890)~~Efavaleukin alfa		~~Cardiovascular~~Systemic lupus erythematosus; Ulcerative colitis
LUMAKRAS/LUMYKRAS		NSCLC monotherapy; Other solid tumors with KRAS G12C mutations
Ordesekimab		Celiac disease
Rozibafusp alfa ~~(formerly AMG 570)~~		Systemic lupus erythematosus
~~Sotorasib~~Tarlatamab		~~Advanced colorectal~~Small cell lung cancer
	~~Other solid tumors with~~ ~~KRAS G12C~~ ~~mutations~~
~~Tezepelumab~~TEZSPIRE		Chronic obstructive pulmonary ~~disease~~disease; Chronic spontaneous urticaria
AMG ~~714/PRV-015~~133		~~Celiac disease~~Obesity

Phase 1 programs
~~Efavaleukin alfa (formerly AMG 592)~~Acapatamab		~~Inflammatory diseases~~Prostate cancer
Bemarituzumab		NSCLC and other tumors
Emirodatamab		Acute myeloid leukemia
Latikafusp		Solid tumors
Tarlatamab		Neuroendocrine prostate cancer
AMG 104		Asthma
AMG 119		Small-cell lung cancer
AMG ~~133~~		~~Obesity~~
~~AMG 160~~		~~Prostate cancer~~
~~AMG 171~~		~~Obesity~~
~~AMG~~ 176		Hematologic malignancies
AMG ~~199~~		~~Metastatic gastric and gastroesophageal junction cancer~~
~~AMG 256~~193		Solid tumors
AMG ~~330~~		~~Acute myeloid leukemia~~
~~AMG 397~~		~~Hematologic malignancies~~
~~AMG 404~~199		Solid tumors
AMG ~~427~~340		~~Acute myeloid leukemia~~Prostate cancer
AMG ~~506~~404		Solid tumors
AMG 509		Prostate cancer
AMG ~~594(1)~~ 609		~~Cardiovascular disease~~Nonalcoholic steatohepatitis
AMG 650		Solid tumors
AMG ~~673~~651		~~Acute myeloid leukemia~~
~~AMG 701~~		~~Multiple myeloma~~
~~AMG 757~~		~~Small-cell lung~~Colorectal cancer
AMG ~~910~~786		~~Gastric and gastroesophageal junction cancer~~Obesity
AMG 794		Solid tumors
AMG 994		Solid tumors

~~(1)~~
In November 2020, we provided notice to Cytokinetics of termination of our collaboration effective May 20, 2021 and of our intention to transition to them the development and commercialization rights for omecamtiv mecarbil and AMG 594.


Phase 3			Clinical trials investigate the short- and long-term safety and efficacy of our product candidates, compared to commonly used treatments, in a large number of patients who have the disease or condition under study.
Phase 2			Clinical trials investigate side-effect profiles and efficacy of product candidates in a larger patient population than phase 1, but still relatively small, who have the disease or condition under study.
Phase 1			Clinical trials investigate the safety and proper dose ranges of product candidates in a small number of human subjects.

Phase 3 Product Candidate Program Changes

As of February ~~12, 2020,~~8, 2022, we had 1413 phase 3 programs. As of ~~February 2, 2021,~~January 31, 2023, we ~~had 13~~have 18 phase 3 programs, as ~~regulatory approvals were received for three programs, two~~five programs initiated phase 3 ~~studies, two programs initiated biosimilarity studies, one concluded and one termination and transition of program to Cytokinetics.~~studies. These changes are set forth in the following table.

Molecule

~~Disease/condition~~Investigational indication

Program change

~~KYPROLIS~~®

~~Multiple myeloma~~

~~Approved by the FDA~~

~~Otezla~~®

~~Behçet’s disease~~

~~Approved by the FDA~~

~~COVID-19~~

~~Initiated phase 3 study~~

~~RIABNI~~TM

~~Non-Hodgkin’s lymphoma~~

~~Approved by the FDA~~

~~Sotorasib~~LUMAKRAS/LUMYKRAS

~~NSCLC~~Advanced colorectal cancer

Initiated phase 3 study

~~ABP 654~~Olpasiran

~~Psoriasis, psoriatic arthritis and Crohn’s~~Cardiovascular disease

Initiated ~~biosimilarity~~phase 3 study

~~ABP 938~~Otezla

~~Neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy~~Palmoplantar pustulosis

Initiated ~~biosimilarity~~phase 3 study

~~IMLYGIC~~®

~~Metastatic melanoma~~Rocatinlimab

~~Concluded~~Atopic dermatitis

Initiated phase 3 study

~~Omecamtiv mecarbil~~TEZSPIRE

~~Chronic heart failure~~Eosinophilic esophagitis

~~Concluded; no longer pursuing our marketing application with the FDA and EC~~Initiated phase 3 study~~(1)~~

~~(1)~~In November 2020, we provided notice to Cytokinetics of termination of our collaboration effective May 20, 2021 and of our intention to transition to them the development and commercialization rights for omecamtiv mecarbil and AMG 594.

~~Based on our approval pathway that did not require phase 3 study, in January 2021, Nplate~~® ~~was approved by the FDA for treatment of hematopoietic syndrome of acute radiation syndrome.~~

Phase 3 Product Candidate Patent Information

The following table describes our composition-of-matter patents that have been issued thus far for our product candidates in phase 3 development that have yet to be approved for any indication in the United States or the EU. Patents for products already approved for one or more indications in the United States or the EU but that are currently undergoing phase 3 clinical trials for additional indications have been previously described. See Marketing, Distribution and Selected Marketed Products—Patents.

Molecule

Territory

General subject matter

Estimated expiration*

~~Sotorasib~~

~~U.S.~~

~~Compound~~

~~2038~~

~~Tezepelumab~~Bemarituzumab

U.S.

Polypeptides

2029

Europe

Polypeptides

~~2028~~2029

Olpasiran

U.S.

Compounds

2036

Europe

Compounds

2036

Rocatinlimab

U.S.

Polypeptides

2027

Europe

Polypeptides

2026

* Patent expiration estimates are based on issued patents, which may be challenged, invalidated or circumvented by competitors. The ~~patent expiration~~ estimates do not include any term adjustments, extensions or supplemental protection certificates that may be obtained in the future and thereby extend these dates. Corresponding patent applications are pending in other jurisdictions. Additional patents may be filed or issued and may provide additional exclusivity for the product candidate or its use.

Phases 3 and 2 Program Descriptions

The following provides additional information about selected product candidates that have advanced into human clinical trials.

AMJEVITA

AMJEVITA is a biosimilar to HUMIRA, which is a monoclonal antibody that inhibits binding of tumor necrosis factor (TNF) alpha to cell surface TNF receptor / TNF-alpha.

Bemarituzumab

Bemarituzumab is a monoclonal antibody that inhibits fibroblast growth factor receptor 2b (FGFR2b). It is being investigated for the treatment of advanced gastroesophageal junction (GEJ) adenocarcinoma.

~~EVENITY~~®

~~EVENITY~~

BLINCYTO

BLINCYTO is an anti-CD19 x anti-CD3 BiTE® molecule. It is being investigated in newly diagnosed adults aged 40 and older with Ph negative B-Cell precursor acute lymphoblastic leukemia (ALL).

Efavaleukin alfa

Efavaleukin alfa is an interleukin (IL)-2 mutein Fc fusion protein. It is being investigated for the treatment of systemic lupus erythematosus and ulcerative colitis.

EVENITY

EVENITY is a ~~humanized~~ monoclonal antibody that inhibits the action of sclerostin. It is being evaluated as a treatment for male ~~osteoporosis.~~osteoporosis. EVENITY® is being developed in collaboration with UCB.

KYPROLIS

~~IMLYGIC~~®

~~IMLYGIC~~® ~~is an oncolytic immunotherapy derived from herpes simplex virus type 1 (HSV-1). A Phase 3 study evaluating IMLYGIC~~® ~~in combination with pembrolizumab (KEYTRUDA~~®) versus pembrolizumab alone for treatment of unresectable stage IIIB to IVM1c melanoma was stopped for futility after an interim analysis by the Data Monitoring Committee. No new safety signals were observed.

KYPROLIS®

~~KYPROLIS~~® is a small molecule proteasome inhibitor. It is being investigated for weekly dosing in combinations with lenalidomide and dexamethasone for relapsed multiple myeloma.

LUMAKRAS/LUMYKRAS

LUMAKRAS/LUMYKRAS is a KRASG12C small molecule inhibitor. It is being investigated as treatment for a variety of solid tumors, including NSCLC, colorectal cancer and other solid tumor cancers.

In February 2022, we announced the presentation of efficacy and safety data from the CodeBreaK 100 Phase 1/2 trial in patients with KRAS G12C–mutated advanced pancreatic cancer who received LUMAKRAS/LUMYKRAS.

In April 2022, we announced the presentation of long-term efficacy and safety data from the CodeBreaK 100 Phase 1/2 trial in patients with KRAS G12C–mutated advanced NSCLC who received LUMAKRAS/LUMYKRAS.

In August ~~2020,~~2022, we announced that the ~~FDA approved~~global Phase 3 CodeBreaK 200 trial evaluating once daily oral LUMAKRAS/LUMYKRAS met its primary endpoint of PFS, demonstrating statistical significance and superiority over standard-of-care chemotherapy, intravenous docetaxel. The first randomized clinical trial for a KRASG12C inhibitor assessed the ~~expansion~~efficacy and safety of LUMAKRAS/LUMYKRAS in 345 previously treated patients with KRAS G12C–mutated NSCLC who had received at minimum, prior platinum-based doublet chemotherapy and checkpoint inhibitor therapy.

In September 2022, we announced detailed results from the global Phase 3 CodeBreaK 200 trial, which showed once-daily oral LUMAKRAS/LUMYKRAS led to significantly superior PFS (primary endpoint) and a significantly higher ORR (a key secondary endpoint) in patients with KRAS G12C–mutated NSCLC, compared with intravenous chemotherapy, docetaxel. We also announced updated data from its Phase 1b CodeBreaK 101 study, one of the ~~KYPROLIS~~® ~~U.S. prescribing information to include its use~~most comprehensive global clinical development programs in ~~combination~~patients with ~~DARZALEX~~® ~~plus dexamethasone in two dosing regimens—once weekly~~KRAS G12C–mutated colorectal cancer. These data show that combining LUMAKRAS/LUMYKRAS with Vectibix, Amgen's monoclonal anti-epidermal growth factor receptor (anti-EGFR) antibody, demonstrated encouraging efficacy and ~~twice weekly—~~safety.

Nplate

Nplate is a thrombopoietin receptor agonist (TPO-RA). It is being investigated for the treatment of ~~patients with relapsed or refractory multiple myeloma who have received one to three previous lines of therapy.~~chemotherapy-induced thrombocytopenia (CIT).

~~Nplate~~®Olpasiran

~~Nplate~~®Olpasiran is ~~a thrombopoietin receptor agonist.~~an siRNA that lowers Lp(a). It is being investigated in phase 3 ~~studies for chemotherapy-induced thrombocytopenia.~~

In December, the European Commission approved an expanded indication for use in adult patients who have had immune thrombocytopenia for 12 months or less and who have had an insufficient response to corticosteroids or immunoglobulins.

~~As noted above, the FDA has approved Nplate~~®for the treatment of ~~hematopoietic syndrome~~ASCVD.

In November 2022, we announced positive end-of-treatment data from the Phase 2 OCEAN(a)-DOSE study evaluating olpasiran in adult patients with Lp(a) levels over 150 nmol/L and a history of ~~acute radiation syndrome.~~1ASCVD. The study was designed to assess safety, tolerability and optimal dose of olpasiran in adults with established ASCVD to reduce Lp(a).

~~OLPASIRAN~~Ordesekimab

~~Olpasiran~~Ordesekimab is a ~~small interfering RNA (siRNA)~~monoclonal antibody that ~~lowers lipoprotein(a), also known as Lp(a).~~inhibits the action of IL-15. It is being investigated ~~in phase 2~~ for the treatment of ~~atherosclerotic CV disease.~~celiac disease and is being developed in collaboration with Provention Bio, Inc.

~~Otezla~~®

Otezla®

Otezla is a small molecule that inhibits PDE4. It is being investigated in phase 3 studies for the treatment of patients with ~~mild-to-moderate plaque psoriasis,~~moderate-to-severe genital psoriasis. It is also being investigated in a phase 2 study for treatment of palmoplantar pustulosis.

In September 2022, we announced results from two significant Phase 3 clinical studies of oral Otezla, demonstrating efficacy in pediatric patients with moderate-to-severe ~~genital~~plaque psoriasis and in ~~collaboration with some of the members of the COVID R&D Alliance, adult patients hospitalized with COVID-19.~~

~~In May 2020, we announced positive results from the ADVANCE trial, a phase 3, multicenter, randomized, placebo-controlled, double-blind study to assess the efficacy of Otezla~~® in adults with ~~mild-to-moderate plaque~~moderate-to-severe genital psoriasis. ~~The study showed that oral Otezla~~® 30 mg twice daily achieved a statistically significant improvement, compared with placebo, in the primary endpoint of the sPGA response at week 16. In addition, the week 16 secondary endpoints of achieving at least 75% improvement from baseline in the percent of affected body surface area (BSA), change in BSA total score from baseline and change in Psoriasis Area and Severity Index (PASI) total score from baseline were each also statistically significant for the treatment effect of Otezla® ~~compared with placebo.~~

Repatha

Repatha®

~~Repatha~~® is a human monoclonal antibody that inhibits PCSK9. It is being investigated as a treatment for ~~atherosclerotic CV disease~~ASCVD in high-risk patients with high ~~low-density lipoprotein cholesterol (LDL-C)~~LDL-C without prior heart attack or stroke.

In ~~March 2020,~~2022, we ~~announced positive~~presented results from the ~~BEIJERINCK study evaluating~~Repatha OLE studies to the ~~efficacy~~Phase 3 FOURIER CV outcomes trial. The studies were designed to assess the long-term safety and ~~safety~~tolerability of Repatha® in ~~patients who are human immunodeficiency virus-positive (HIV+) and have high LDL-C despite stable background lipid-lowering therapy. The study demonstrated~~adults with clinically evident ASCVD.

Rocatinlimab

Rocatinlimab is a monoclonal antibody that ~~treatment with Repatha~~® ~~significantly reduced LDL-C.~~

~~RIABNI~~TM

~~RIABNI~~TM~~, a biosimilar candidate to Rituxan~~®~~/MabThera~~® ~~(rituximab), is an anti-CD20 monoclonal antibody.~~inhibits OX-40. It is being investigated ~~in a phase 3 study for treatment of rheumatoid arthritis. The reference-product primary conditions are non-Hodgkin’s lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis.~~

1 Funding and execution of the pivotal study was provided by the National Institute of Allergy and Infectious Diseases (NIAID) and the Priority Review regulatory submission was conducted in partnership with the Biomedical Advanced Research and Development Authority (BARDA).

~~In December 2020, we announced that the FDA had approved RIABNI~~TM for the treatment of ~~adult patients~~moderate-to-severe atopic dermatitis. Rocatinlimab is being developed in collaboration with ~~non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis (Wegener’s granulomatosis), and microscopic polyangiitis. RIABNI~~TM ~~launched in the United States in January 2021.~~KKC.

Rozibafusp alfa

Rozibafusp alfa is a novel ~~bispecific~~ antibody-peptide conjugate that simultaneously blocks the ~~B lymphocyte stimulator~~B-cell activating factor (BAFF) and inducible costimulatory ligand (ICOSL)activity. It is being investigated as a treatment for systemic lupus erythematosus.

~~Sotorasib~~Tarlatamab

~~Sotorasib~~Tarlatamab is a ~~KRAS~~ half-life extended (HLE) anti- DLL3 x anti-CD3 BiTE~~G12C~~® ~~small molecule inhibitor.~~molecule. It is being investigated ~~as a treatment for a variety of solid tumors, including NSCLC, colorectal cancerand other solid tumor cancers.~~

~~In December 2020, we announced that the FDA had granted Breakthrough Therapy designation for sotorasib~~ for the treatment of ~~patients with locally advanced or metastatic NSCLC with~~ ~~KRASG12C~~ mutation as determined by an FDA-approved test, following at least one prior systemic therapy. The sotorasib application is being reviewed under the FDA’s RTOR pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible.small cell lung cancer.

~~In January 2021, we announced phase 2 results from the CodeBreaK 100 clinical study, evaluating sotorasib in 126 patients with~~ ~~KRASG12C-mutant~~ advanced NSCLC, who had failed a median of two prior lines of anticancer therapies (immunotherapy and/or chemotherapy). Sotorasib demonstrated a confirmed ORR (primary end point) and disease control rate of 37.1% and 80.6%, respectively, a median duration of response of 10 months and median progression-free survival of 6.8 months. Patients were treated with sotorasib 960 mg once daily orally.TEZSPIRE

~~Tezepelumab~~

~~Tezepelumab~~TEZSPIRE is a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin. It is being evaluated in phase 3 studies as a treatment for severe ~~asthma.~~asthma and chronic rhinosinusitis with nasal polyps. It is also being investigated in phase 2 studies as a treatment for chronic obstructive pulmonary ~~disease. Tezepelumab~~disease and chronic spontaneous urticaria. TEZSPIRE is being developed jointly in collaboration with AstraZeneca.

In ~~November 2020,~~February 2022, we announced ~~positive~~ results from a pooled post hoc analysis of the ~~registrational phase~~pivotal NAVIGATOR Phase 3 ~~NAVIGATOR trial,~~and PATHWAY Phase 2b trials that showed TEZSPIRE demonstrated reductions in ~~which~~ the ~~investigational medicine tezepelumab demonstrated a statistically significant reduction in exacerbations compared to placebo~~annualized asthma exacerbation rate (AAER) across biomarker subgroups of patients with severe asthma.

A Phase 3 study of TEZSPIRE in patients with severe asthma. The NAVIGATOR trial met the primary endpoint with tezepelumab added to SoC, demonstrating a statistically significant and clinically meaningful reduction compared to placebo plus SoC in the AAER over 52 weeks in the overall patient population. SoC consisted of medium- or high-dose ICS plus at least one additional controller medication with or without OCS.eosinophilic esophagitis has started.

In December 2020, we announced that the SOURCE trial had not met the primary endpoint of a statistically significant reduction in the daily OCS dose, without loss of asthma control, with tezepelumab compared to placebo. The results of this trial have no impact on our submission plans.AMG 133

AMG ~~714/PRV-015~~

~~AMG 714/PRV-015~~133 is a ~~human monoclonal antibody that binds to interleukin-15.~~gastric inhibitory polypeptide receptor (GIPR) antagonist and glucagon-like peptide 1 (GLP-1) receptor agonist. It is being investigated for the treatment of ~~celiac disease and is being developed in collaboration with Provention Bio.~~obesity.

ABP 654

ABP 654, a biosimilar candidate to STELARA,® ~~(ustekinumab),~~ is a monoclonal antibody that inhibits ~~interleukin-12~~IL-12 and ~~interleukin-23.~~IL-23. It is being investigated in a phase 3 study for biosimilarity to ~~STELARA~~®.STELARA. The reference-product primary conditions are psoriasis, psoriatic arthritis and Crohn’s disease.

In April 2022, we announced preliminary results from a Phase 3 study evaluating the efficacy and safety of ABP 654 compared to STELARA in adult patients with moderate-to-severe plaque psoriasis. The study met the primary efficacy endpoint, demonstrating no clinically meaningful differences between ABP 654 and STELARA.

ABP 938

ABP 938, a biosimilar candidate to EYLEA,® ~~(aflibercept),~~ is a vascular endothelial growth factor receptor (VEGFR) Fc fusion protein. It is being investigated in a phase 3 study for ~~neovascular (wet) age-related macular degeneration (AMD).~~biosimilarity to EYLEA. The reference-product primary conditions are wet ~~AMD,~~age-related macular degeneration (AMD), macular edema following retinal vein occlusion, diabetic macular edema and diabetic retinopathy.

2221

ABP 959

ABP 959, a biosimilar candidate to SOLIRIS,® ~~(eculizumab),~~ is a monoclonal antibody that specifically binds to the complement protein C5. It is being investigated in a phase 3 study for ~~PNH.~~biosimilarity to SOLIRIS. The reference-product primary conditions are PNH and atypical hemolytic uremic syndrome (aHUS).

In August 2022, we announced positive top-line results from the DAHLIA study, a randomized, double-blind, active-controlled, two-period crossover Phase 3 study evaluating the efficacy and safety of ABP 959, a biosimilar candidate to SOLIRIS, compared with SOLIRIS in adult patients with PNH.

Business Relationships

From time to time, we enter into business relationships, including joint ventures and collaborative arrangements, for the R&D, manufacture and/or commercialization of products and/or product candidates. In addition, we acquire product and R&D technology rights and establish R&D collaborations with third parties to enhance our strategic position within our industry by strengthening and diversifying our R&D capabilities, product pipeline and marketed-product base. These arrangements generally provide for nonrefundable upfront license fees, development and commercial-performance milestone payments, cost sharing, ~~royalty payments~~royalties and/or profit sharing. The activities under these collaboration agreements are performed with no guarantee of either technological or commercial success, and each is unique in nature.

Trade secret protection for our unpatented confidential and proprietary information is important to us. To protect our trade secrets, we generally require counterparties to execute confidentiality agreements upon commencement of a business relationship with us. However, others could either develop independently the same or similar information or unlawfully obtain access to our information.

BeiGene, Ltd.

OnIn January 2, 2020, we acquired ~~a 20.5%~~an equity stake in BeiGene ~~Ltd. (BeiGene)~~ for approximately $2.8 billion in cash as part of a collaboration to expand our oncology presence in China. For additional information regarding our equity investment in BeiGene, see Part IV—Note 9, Investments, to the Consolidated Financial Statements. Under the collaboration, BeiGene ~~commenced~~began selling XGEVA® in 2020, BLINCYTO in 2021 and ~~will commercialize~~ KYPROLIS® ~~and BLINCYTO~~® in 2022 in China, and Amgen ~~will share~~shares profits and losses equally during the initial product-specific commercialization periods; thereafter, product rights may revert to Amgen, and Amgen will pay royalties to BeiGene on sales in China of such products for a specified period. Amgen manufactures and supplies the collaboration products to BeiGene.

In addition, we ~~will~~ jointly develop a portion of our oncology portfolio with BeiGene, ~~sharing~~which shares in global R&D costs by providing cash and development services of up to $1.25 billion. Upon regulatory approval, BeiGene will assume commercialization rights in China for a specified period, and Amgen and BeiGene will share profits equally until certain of these product rights revert to Amgen. Upon return of the product rights, Amgen will pay royalties to BeiGene on sales in China for a specified period. For product sales outside of China, Amgen will also pay ~~BeiGene royalties.~~royalties to BeiGene.

~~Novartis~~AstraZeneca plc

We are in a collaboration with ~~Novartis~~AstraZeneca for the development and commercialization of TEZSPIRE. Under our collaboration, both companies share global costs, profits and losses equally after payment by AstraZeneca of a mid-single-digit royalty to ~~jointly develop~~Amgen. AstraZeneca leads global development, and ~~commercialize Aimovig~~®~~. In the United States,~~both Amgen and ~~Novartis~~AstraZeneca jointly ~~develop and collaborate on the commercialization of Aimovig~~®.commercialize TEZSPIRE in North America. In North America, Amgen, as the principal, recognizes product sales of ~~Aimovig~~®TEZSPIRE in the United States, ~~shares U.S. commercialization costs with Novartis~~ and ~~pays Novartis a significant royalty on net sales in~~AstraZeneca, as the ~~United States. Novartis holds global co-development rights and exclusive commercial rights outside the United States and Japan for Aimovig~~®~~. Novartis pays Amgen double-digit royalties on net~~principal, recognizes product sales of ~~the product~~TEZSPIRE in the Novartis-exclusive territories and funds a portion of global R&D expenses. In addition, Novartis will make a payment to Amgen of up to $100 million if certain commercial and expenditure thresholds are achieved with respect to Aimovig® ~~in the United States.~~Canada. AstraZeneca leads commercialization for TEZSPIRE outside North America. Amgen manufactures and supplies ~~Aimovig~~®TEZSPIRE worldwide.

UCB

We are ~~currently involved~~ in ~~litigation~~a collaboration with ~~Novartis over our collaboration agreements~~UCB for the development and commercialization of ~~Aimovig~~®EVENITY. Under our collaboration, UCB has rights to lead commercialization for EVENITY in most countries in Europe and China (excluding Hong Kong). ~~See Part IV—Note 19, Contingencies~~Amgen, as the principal, leads commercialization for EVENITY and ~~commitments,~~recognizes product sales in all other territories, including the United States. Global development costs and commercialization profits and losses related to the ~~Consolidated Financial Statements.~~

~~Bayer HealthCare LLC~~

Wecollaboration are ~~in a licensing arrangement with Bayer HealthCare LLC (Bayer) for Nexavar~~®~~. In February 2020, we amended the terms of our agreement with Bayer, which transferred all of our operational responsibilities outside the United States to Bayer, including commercial~~shared equally. Amgen manufactures and medical affairs activities. Prior to the amendment of the agreement, we shared equally in the profits outside the United States, excluding Japan. In lieu of this profit share, Bayer now pays us a royalty on sales of Nexavar® ~~at a percentage rate in the low 30s. The rights to develop and market Nexavar~~® ~~in Japan are reserved to Bayer. In the United States, Bayer pays us a royalty on sales of Nexavar~~® ~~at a percentage rate in the high 30s.~~

~~DaVita Inc.~~

In January 2017, we entered into a six-year supply agreement with DaVita Inc. (DaVita), which superseded the previously existing, seven-year supply agreement that commenced in 2012. Pursuant to the 2017 agreement, we supply EPOGEN® ~~and Aranesp~~® in amounts necessary to meet specified annual percentages of DaVita’s and its affiliates’ requirements for erythropoiesis-stimulating agents (ESAs) used in providing dialysis services in the United States and Puerto Rico. Such percentages vary during the term of the agreement, but in each year are at least 90%. The agreement expires in 2022. The agreement may be terminated by either party before expiration of its term in the event of certain breaches of the agreement by the other party.supplies EVENITY worldwide.

For financial information ~~concerning~~about our significant collaborative arrangements, see Part IV—Note 8, Collaborations, to the Consolidated Financial Statements.

Human Capital Resources

Overview

Amgen’s approach to human capital resource management starts with our mission to serve patients. We strive to serve patients by transforming the promise of science and biotechnology into therapies that have the power to restore health or save lives. The way we approach our business is guided by our Amgen Values:


Amgen Values
Be Science-Based	Compete Intensely and Win	Create Value for Patients, Staff and Stockholders	Be Ethical
Trust and Respect Each Other	Ensure Quality	Work in Teams	Collaborate, Communicate and Be Accountable

Our staff are also guided by the Company’s Code of Conduct, which is designed to help every person who does business on our behalf worldwide (including all staff, management, consultants, contract workers and temporary workers) to understand what is expected of them.

Our industry exists in a complex regulatory and reimbursement environment. The unique demands of our industry, together with the challenges of running an enterprise focused on the discovery, development, manufacture and commercialization of innovative medicines, ~~require talent that is~~requires a highly ~~educated and/or has significant industry experience. Additionally, for certain key functions, we require specific scientific expertise to oversee~~engaged and ~~conduct R&D activities and the complex manufacturing requirements for biopharmaceutical products.~~committed workforce.

As of December 31, ~~2020,~~2022, Amgen had approximately ~~24,300~~25,200 staff members in over 50 countries, and we have had relatively low global turnover ~~rates.~~rates compared to available industry information. We also supplement our workforce with independent contractors, contingent workers and temporary workers, as needed. Outside of the United States, some of our employees are represented by unions or works councils. We consider our staff relations to be ~~good;~~good, supported by ~~our~~ regular assessments of staff engagement ~~assessments, with~~ surveys on a wide range of topics (including ~~engagement in the COVID-19 environment,~~flexible work environments, diversity, inclusion and belonging, and ~~ethics)~~maintaining a culture of compliance). We discuss the results of these surveys with our workforce and our Board of Directors. Reflecting our staff members’ desire to retain flexibility to work virtually as COVID-19 related restrictions eased and sites became more accessible, we implemented a flexible workspace initiative that enables many employees to work together with their manager to determine the location that best enables their work at hand, supporting virtual work as well as coming on site.

Compensation, Benefits and Development

Our approach to employee compensation and benefits is designed to deliver cash, equity and benefit programs that are competitive with those offered by leading companies in the biotechnology and pharmaceutical industries, and to attract, motivate and retain talent with a focus on encouraging performance, promoting accountability and adherence to Company values and alignment with the interests of the Company’s shareholders.

Our base pay program aims to compensate staff members relative to the value of the contributions of their role, which takes into account the skills, knowledge and abilities required to perform each position, as well as the experience brought to the job. We also provide annual incentive programs to reward our staff in alignment with achievement of Company-wide goals that are established annually and designed to drive aspects of our strategic priorities that support and advance our strategy across our Company. The majority of our staff members are also eligible for the grant of equity awards under our long-term incentive program that are designed to align the ~~experience~~interests of ~~these~~our staff members with ~~that~~those of our shareholders. For senior level staff, a significant proportion of equity award value is based on company performance.

All staff also participate in a regular performance measurement process ~~that aligns pay to performance and~~ through which staff receive performance and development ~~feedback.~~ feedback, and pay is aligned to performance. The Amgen Values and leadership behaviors are an integral part of the performance assessments of our staff members, and these evaluations serve as an important information tool and basis for compensation decisions.

To support the development of our staff, we provide a variety of programs, including leadership development programs, classroom-based and virtual instructor-led courses, and self-paced learning ~~options.~~options as well as mentoring, networking and coaching opportunities.

Our benefit programs are also generally broad-based, promote health and overall well-being and emphasize saving for retirement. All regular U.S. staff members are eligible to participate in the same core health and welfare and retirement savings plans. Other U.S. employee benefits include medical plans, dental plans, adoption assistance, paid parental leave programs, access to childcare, employee assistance programs, employee stock purchase plan, flexible spending accounts, life, long-term care and business travel accident insurance, short and long-term disability benefits, wellness benefits and work-life resources and referrals. Comparable programs and benefits are available globally, with the same health and well-being intent, consistent with statutory requirements.

Our Compensation and Management Development Committee provides oversight of our compensation plans, policies and programs.

Safety and Wellness and Our Response to the Evolving COVID-19 Pandemic

Creating a safe and healthy workplace for our staff is aan important priority at Amgen. Our goal is to have a world class safety record through safety leadership, risk management practices and integrating safety throughout our business processes. To foster our safety culture, we implement a comprehensive safety program and reinforce desired safety behaviors, driving to understand and mitigate the root cause of safety incidents and manage and control variability. We use leading indicators to assess the effectiveness of our safety programs and make course corrections as needed. Additionally, we perform formal executive management review of functional safety performance for Operations, Global Commercial Operations and R&D on a quarterly basis with a focus on identifying early signals and taking action to drive continuous improvement. ~~Based on our 2019 performance, compared to a benchmark of twelve companies~~

In 2022, in ~~the pharmaceutical industry, Amgen was in the quartile with the lowest injury rate.~~

In response to the evolving requirements of the COVID-19 pandemic, to continue to maintain staff safety while enabling greater flexibility for Amgen sites and ~~as part of~~enhance efficiencies, we began shifting to a decentralized model for COVID-19 decision-making, empowering our ~~commitment~~local teams to ~~work to ensure the~~adjust COVID-19 safety ~~and well-being of our employees, we have activated our applicable business continuity plans, including having those of our~~employees who are able to work from home to do so since mid-March 2020. For employees returning to the workplace and the field, we have also taken additional safety measures, including implementing occupancy limits, restricting business travel, providing and requiringguidance for their individual sites or regions (such as the use of masks and other personal protective equipment, occupancy limits, and temperature ~~screening~~check and ~~COVID-19~~ testing, based on local regulations and risk assessments of local epidemiology criteria). We will continue to ~~access our workplaces.~~learn and adapt this approach as needed for the future.

Our Corporate Responsibility and Compliance Committee provides general oversight of our safety programs and initiatives, while our Board of Directors, as a whole, has overseen our specific responses to the COVID-19 pandemic.

Diversity, Inclusion and Belonging

We believe that a diverse and inclusive culture fosters innovation, which supports our ability to serve patients. Further, we also believe our global presence is strengthened by having a workforce that reflects the diversity of the patients we serve. It is with these beliefs in mind that we have continued to strengthen and grow our culture of diversity, inclusion and belonging. Our ~~internal efforts include, in 2019, establishing a~~ Diversity, Inclusion and Belonging Council ~~chaired~~is led by our ~~Chief Executive Officer. In 2020, we implemented~~executive leadership and is responsible for overseeing our strategy to further a ~~global unconscious bias training program,~~diverse and ~~launched~~inclusive workplace. We offer a ~~portal devoted to~~variety of diversity, inclusion and belonging training and learning programs and have continued to launch enhanced tools and resources that ~~includes learning~~guide staff on the role they play in creating diversity, inclusion and ~~resources.~~belonging throughout the organization. Further, we ~~are leveraging~~continue to incorporate diversity, inclusion and belonging considerations into our business operations, including clinical trial design, procurement and site selection.

Each of Amgen’s Employee Resource Groups ~~(listed below)~~is sponsored by senior executive leadership. Our Employee Resource Groups promote leadership, development and belonging for members while also working to ~~represent~~impact our business by leading business initiatives and ~~support~~providing diverse perspectives and experience. In 2022, Amgen launched its newest global Employee Resource Group called Recognition of Indigenous Peoples, Values and Environmental Resources, or RIVER, to share and continue the ~~diversity~~traditions, values and culture of ~~Amgen staff:~~Indigenous people.


Global Employee Resource Groups
Amgen Asian Association (AAA)			Amgen Black Employee Network (ABEN)
Ability Bettered through Leadership and Education (ABLE), a resource group for those with disabilities, visible and invisible, including those conditions also experienced by the ~~physically or cognitively disabled~~patients that Amgen serves
Amgen Early Career Professionals (AECP)			Amgen ~~Indian Subcontinent~~International Network ~~(AISN)~~(AIN)
Amgen Latin Employee Network (ALEN)			Amgen LGBTQ and Allies Network (PRIDE)
Amgen South Asian Network (ASAN)			Amgen Veterans Employees Network (AVEN)
Recognition of Indigenous Peoples, Values and Environmental Resources (RIVER)
Women Empowered to be Exceptional (WE2)
Women in ~~Information Systems~~STEM Enrichment (WISE)

Building on the successful adoption of our 2021 ESG goal under our annual incentive plan, we are driving leadership ownership and accountability for diversity, inclusion and belonging deeper in the organization with an enhanced ESG goal for 2022 designed to advance our progress on key ESG initiatives, including by expanding the number of leaders accountable for establishing, documenting and executing on diversity, inclusion and belonging action plans.

As of December 31, 2022, women comprised over 52% of our global workforce, and ethnic minorities accounted for approximately 52% of our U.S. and Puerto Rico-based workforce. In areas of underrepresentation, we develop plans with a goal of bringing our representation in line with ~~availability, and we also~~availability. We engage in outreach efforts to attract, retain and advance more women and minorities in our workforce. For example, we have worked to enhance our diverse candidate recruiting pool by developing relationships with organizations that can serve as a source of diverse candidates, such as the National Black MBA Association and ~~National Sales Network,~~Society of Women in Engineering, as well as historically black colleges and universities. In 2021, a fellowship program between Amgen and Howard University was established to expand the talent pool and diversify ranks in research and development.

Additionally, ~~at the end of 2020,~~ we ~~became~~are a founding member of OneTen, a coalition ~~of 35~~ of the world’s largest, best-known companies, that aims to hire one million Black Americans (with a specific focus on those without four-year college degrees) into good-paying, family-sustaining jobs over the next ten years. Amgen is taking a leadership role in the greater Los Angeles region, where the company is headquartered, to help expand the coalition of OneTen organizations that share our desire to offer opportunities to diverse talent, and we developed an in-house apprenticeship program in support of our OneTen commitment. Other examples of actions that we are taking in this area include increased investment and participation in the Healthcare Businesswomen’s Association (a global organization focused on development and business networking for women in healthcare) and the ~~University of California, Los Angeles (UCLA)~~UCLA Anderson School of Management ~~women’s~~ leadership ~~program.~~advancement programs for women and underrepresented talent.

Our 2021 Consolidated EEO-1 Report can be viewed on our website at www.amgen.com (the website address is not intended to function as a hyperlink, and the information contained in our website is not intended to be a part of this filing).

For 2022, our Compensation and Management Development Committee oversaw our labor and employment policies, programs and initiatives, including those relating to diversity, inclusion and belonging.

In an effort to provide additional transparency into the makeup of our workforce, we intend to disclose our 2020 Consolidated EEO-1 Report after our submission of the report to the U.S. Equal Employment Opportunity Commission.

~~Our Corporate Responsibility and Compliance Committee provides oversight of our policies, programs and initiatives focusing on workforce diversity and inclusion.~~

Information about Our Executive Officers

The executive officers of the Company as of February ~~8, 2021,~~9, 2023, are set forth below.

Mr. Robert A. Bradway, age ~~58,~~60, has served as a director of the Company since 2011 and Chairman of the Board of Directors since 2013. Mr. Bradway has been the Company’s President since 2010 and Chief Executive Officer since 2012. From 2010 to 2012, Mr. Bradway served as the Company’s President and Chief Operating Officer. Mr. Bradway joined the Company in 2006 as Vice President, Operations Strategy, and served as Executive Vice President and Chief Financial Officer from 2007 to 2010. Prior to joining the Company, Mr. Bradway was a Managing Director at Morgan Stanley in London, where, beginning in 2001, he had responsibility for the firm’s banking department and corporate finance activities in Europe. Mr. Bradway has been a director of The Boeing Company, an aerospace company and manufacturer of commercial airplanes, defense, space and securities systems, since 2016. He has served on the board of trustees of the University of Southern California since 2014. From 2011 to 2017, Mr. Bradway was a director of Norfolk Southern Corporation, a transportation company.

Mr. Murdo Gordon, age ~~54,~~56, became Executive Vice President, Global Commercial Operations, in 2018. Prior to joining the Company, Mr. Gordon was Chief Commercial Officer at ~~BMS~~Bristol Myers Squibb Company (BMS), a pharmaceutical company, from 2016 to 2018. Mr. Gordon served as Head of Worldwide Markets at BMS from 2015 to 2016. Prior to this, Mr. Gordon served in a variety of leadership roles at BMS for more than 25 years.

Mr. Jonathan P. Graham, age ~~60,~~62, became Executive Vice President, General Counsel and Secretary in 2019. Mr. Graham joined the Company in 2015. From 2015 to 2019, Mr. Graham was Senior Vice President, General Counsel and Secretary. Prior to joining Amgen, from 2006 to 2015, Mr. Graham was Senior Vice President and General Counsel at Danaher Corporation. From 2004 to 2006, Mr. Graham was Vice President, Litigation and Legal Policy, at General Electric Company (GE). Prior to GE, Mr. Graham was a partner at Williams & Connolly LLP.

Mr. Peter H. Griffith, age ~~62,~~64, became Executive Vice President and Chief Financial Officer in 2020. Mr. Griffith joined the Company in 2019 as Executive Vice President, Finance. Prior to joining Amgen, Mr. Griffith was President of Sherwood Canyon Group, ~~LLC.~~LLC, a private equity firm. From 1997 to 2019, Mr. Griffith was a partner at EY, an accounting and professional services firm, and served in a variety of senior leadership roles, with his last position being Global Vice Chair, Corporate Development. Prior to EY, Mr. Griffith was a Managing Director and head of the investment banking division of Wedbush Securities Inc.

Ms. Nancy A. Grygiel, age ~~53,~~55, became Senior Vice President and Chief Compliance Officer in 2020. Ms. Grygiel joined the Company in 2015. From 2016 to 2020, Ms. Grygiel was Vice President, Compliance. Prior to joining Amgen, from 2011 to 2015, Ms. Grygiel served as Vice President, Compliance, Corporate & International, at Allergan, Inc. (Allergan). Prior to Allergan, Ms. Grygiel held several management positions at Mylan Pharmaceuticals, Inc.

Ms. ~~Lori A. Johnston,~~Rachna Khosla, age 56, became Executive Vice President, Human Resources, in 2019. From 2016 to 2019, Ms. Johnston served as the Company’s Senior Vice President, Human Resources. From 2012 to 2016, Ms. Johnston was Executive Vice President and Chief Administrative Officer of Celanese Corporation (Celanese). Prior to Celanese, Ms. Johnston served in a series of progressive leadership roles at Amgen from 2001 to 2012, with her last position being Vice President, Human Resources. Prior to joining the Company, Ms. Johnston held human resources and other positions at Dell Inc.

~~Mr. David A. Piacquad, age 64,~~50, became Senior Vice President, Business Development, in ~~2014. Mr. Piacquad~~2021. Ms. Khosla joined the Company in ~~2010 and served~~2013 as ~~Vice President, Strategy and~~ Corporate Development ~~until his appointment~~Director. From 2018 to ~~the role of~~2021, Ms. Khosla was Vice President, Business Development, ~~in 2014.~~and from 2016 to 2018, was Executive Director, Business Development. Prior to joining the Company, ~~from 2009~~Ms. Khosla was a Director at Lazard Ltd. (Lazard) responsible for healthcare mergers and acquisitions. Prior to ~~2010,~~ Lazard, Ms. Khosla had various roles at Credit Suisse Group AG, Sanofi Aventis, Aventis Capital, J.P. Morgan Chase & Co., and Salomon Brothers, Inc.

Mr. ~~Piacquad was Principal of David A. Piacquad Consulting LLC. From 2006 to 2009, Mr. Piacquad served as~~Derek Miller, age 50, became Senior Vice President, ~~Business Development~~Human Resources, in 2022. Mr. Miller joined the Company in 2003 and ~~Licensing, at Schering-Plough Corporation (Schering-Plough).~~has held human resources leadership roles supporting each of the Company’s major business functions. From 2020 to 2022, Mr. Miller was Vice President, Global Total Rewards, and from 2018 to 2020, was Vice President, Human Resources. From 2015 to 2018, Mr. Miller was an Executive Director, Human Resources. Prior to ~~Schering-Plough,~~2015, Mr. ~~Piacquad~~Miller served as a Senior Manager in ~~a series of leadership roles in finance~~the Human Resources organization, before his promotion to Director, Human Resources, and ~~business development at J&J, with his last position being Vice President, Ventures and Business Development.~~

then to Strategy Director.

Dr. David M. Reese, age ~~58,~~60, became Executive Vice President, R&D, in 2018. Dr. Reese joined the Company in 2005 and has held leadership roles in development, medical sciences and discovery research. Dr. Reese was Senior Vice President, Translational Sciences and Oncology, from 2017 to 2018 and Senior Vice President, Translational Sciences, from 2015 to 2017. Prior to joining Amgen, Dr. Reese was director of Clinical Research at the Breast Cancer International Research Group from 2001 to 2003 and a cofounder, president and chief medical officer of Translational Oncology Research International, a not-for-profit academic clinical research organization, from 2003 to 2005. Dr. Reese previously served on the faculty at ~~UCLA~~the University of California, Los Angeles and the University of California, San Francisco.

Mr. Esteban Santos, age ~~53,~~55, became Executive Vice President, Operations, in 2016. Mr. Santos joined the Company in 2007 as Executive Director, Manufacturing Technologies. From 2013 to 2016, Mr. Santos was Senior Vice President, Manufacturing. From 2008 to 2013, Mr. Santos held a number of Vice President roles at the Company in engineering, manufacturing, site operations and drug product. ~~From 2013 to 2016, Mr. Santos was Senior Vice President, Manufacturing.~~ Prior to joining the Company, Mr. Santos served as Site General Manager of ~~J&J’s~~Johnson & Johnson’s (J&J) Cordis operation in Puerto Rico. Prior to J&J, Mr. Santos held several management positions in GE’s industrial and transportation businesses.

Geographic Area Financial Information

For financial information concerning the geographic areas in which we operate, see Part IV—Note 3, Revenues, and Note 11, Property, plant and equipment, to the Consolidated Financial Statements.

Investor Information

Financial and other information about us is available on our website at www.amgen.com. We make available on our website, free of charge, copies of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act as soon as reasonably practicable after we electronically file such material with or furnish it to the U.S. Securities and Exchange Commission (SEC). In addition, we have previously filed registration statements and other documents with the SEC. Any document we file may be inspected without charge at the SEC’s website at www.sec.gov. (These website addresses are not intended to function as hyperlinks, and the information contained in our website and in the SEC’s website is not intended to be a part of this filing.)


Item 1A.			RISK FACTORS

This report and other documents we file with the SEC contain forward-looking statements that are based on current expectations, estimates, forecasts and projections about us, our future performance, our business, our beliefs and our management’s assumptions. These statements are not guarantees of future performance and involve certain risks, uncertainties and assumptions that are difficult to predict. You should carefully consider the risks and uncertainties our business faces. The risks described below are not the only ones we face. Our business is also subject to the risks that affect many other companies, such as employment relations, general economic conditions, geopolitical events and international operations. Further, additional risks not currently known to us or that we currently believe are immaterial may in the future materially and adversely affect our business, operations, liquidity and stock price.

SUMMARY

Risks Related to Economic Conditions and Operating a Global Business, Including During the COVID-19 Pandemic

•The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, manufacturing, supply chains, distribution systems, product development, product sales, business and results of operations.

•A breakdown of our information technology systems, cyberattack or information security breach could compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation.

•Our sales and operations are subject to the risks of doing business internationally, including in emerging markets.

Risks Related to Government Regulations and Third-Party Policies

•Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability.

•Guidelines and recommendations published by various organizations can reduce the use of our products.

•The adoption and interpretation of new tax legislation or exposure to additional tax liabilities could affect our profitability.

•Our business may be affected by litigation and government investigations.

Risks Related to Competition

•Our products face substantial competition and our product candidates are also likely to face substantial competition.

•Our intellectual property positions may be challenged, invalidated or circumvented, or we may fail to prevail in current and future intellectual property litigation.

•We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future.

•Concentration of sales at certain of our wholesaler distributors ~~and at one free-standing dialysis clinic business~~ and consolidation of private payers may negatively affect our business.

Risks Related to Research and Development

•We may not be able to develop commercial products despite significant investments in R&D.

•We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications.

•Our current products and products in development cannot be sold without regulatory approval.

•Some of our products are used with drug delivery or companion diagnostic devices that have their own regulatory, manufacturing and other risks.

•Some of our pharmaceutical pipeline and our commercial product sales rely on collaborations with third parties, which may adversely affect the development and ~~sale~~sales of our products.

•Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions.

Risks Related to Operations

•We perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California; significant disruptions or production failures at these facilities could significantly impair our ability to supply our products or continue our clinical trials.

•We rely on third-party suppliers for certain of our raw materials, medical devices and components.

•Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

•Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives.

•The effects of global climate change and related natural disasters could negatively affect our business and operations.

General Risk Factors

•Global economic conditions may negatively affect us and may magnify certain risks that affect our business.

•Our stock price is ~~volatile~~volatile.

•We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

RISKS RELATED TO ECONOMIC CONDITIONS AND OPERATING A GLOBAL BUSINESS, INCLUDING DURING THE COVID-19 PANDEMIC

The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, manufacturing, supply chains, distribution systems, product development, product sales, business and results of operations.

The novel coronavirus identified in late 2019, SARS-CoV-2, which causes the disease known as COVID-19, is an ongoing global pandemic that has resulted in public and governmental efforts to contain or slow the spread of the disease, including widespread shelter-in-place orders, social distancing interventions, quarantines, travel restrictions and various forms of operational shutdowns. The COVID-19 pandemic and the resulting measures implemented in response to the pandemic are adversely affecting, and isare expected to continue to adversely affect, our business (including our R&D, clinical trials, operations, manufacturing, supply chains, distribution systems, product development and sales activities), the business activities

of our suppliers, customers, third-party payers and our patients. See Our current products and products in development cannot be sold without regulatory approval,; ~~and~~ see also We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications. Due to the pandemic and these measures and their effects, we have experienced, and expect to continue to experience, unpredictable reductions in demand for certain of our products, ~~and~~exacerbated by COVID-19 surges resulting in ~~some cases, have experienced, and could continue to experience, unpredictable increases in demand for certain of our products.~~

Our clinical trials have been, and are expected to continue to be, adversely affected by the COVID-19 pandemic. We have clinical work ongoing at investigational sites across the globe. A number of clinical trial sites, including those in regions experiencing new or resurgent outbreaks of COVID-19, have restricted site visits and imposed restrictions on the initiation of new clinical trialsrepeated shutdowns and/or patient visits to protect both site staff and patients from possible COVID-19 exposure that has stopped or slowed clinical trial activities. In response to the safety concerns related to COVID-19, we have suspended, and will continue to suspend, enrollment and screening in clinical trials where sites are unable to perform clinical trial work due to COVID-19 or there is uncertainty around the ability of sites to ensure subject safety or data integrity. Further, the COVID-19 pandemic has adversely affected, and may continue to adversely affect, our ability to enroll or to continue to enroll certain required post-marketing studies, including pediatric studies. While many of our clinical trial activities have recommenced over the course of 2020, the initial disruption caused by the COVID-19 pandemic to our clinical trials and our clinical trial plans and timelines, and any similar future disruptions (including as a result of the current surge and lockdowns in numerous regions), may have a significant adverse effect on our product development and launches, and, in turn, on future product sales, business and results of operations. For example, to ensure patient safety we initially paused enrollment of our sotorasib Phase 1 combination cohort with Keytruda® and Phase 3 lung cancer study, and such interruptions in enrollment may ultimately affect the timeline of these or other studies. Additionally, while we are investing in research, collaborations and operational support to potentially develop and/or produce treatments for COVID-19, such activities may not result in therapeutic candidates, product approvals, successful production and/or significant commercial value being derived from potential COVID-19-related medicines.

As a result of the COVID-19 pandemic, we have experienced, and expect to continue to experience, regulatory delays, including delays in receiving regulatory advice, reviews of applications, or performance of inspections required for approvals. The pandemic may also result in greater regulatory uncertainty. For example, the FDA and the EMA have issued guidance to provide biopharmaceutical manufacturers greater flexibility in certain regulatory areas, including protocol deviations and adverse event reporting. However, such flexibility may result in greater uncertainty regarding the expectations of such health authorities in relation to this guidance. Additionally, there may be delays in ongoing or new patent office or patent proceedings in the United States or internationally that may delay the outcome of such proceedings. Such delays and disruptions could have a significant adverse effect on our product development and launches, product sales, business and results of operations.

In response to COVID-19, we have activated our applicable business continuity plans, including suspending U.S. in-person meetings and interactions with the healthcare community and professionals in a substantial number of states, suspending, as a general matter, all international business travel and the majority of domestic travel within the United States, and U.S. employees who are able to work from home have been doing so since mid-March 2020. Our ability to perform critical functions and maintain operations have been adversely affected and could continue to be adversely affected as a result of such workforce restrictions, and the COVID-19-related support programs we have put into place for our staff, suppliers and customers have increased, and are expected to continue to increase, our operating expenses and reduce the efficiency of our operations. Notwithstanding such support programs, the COVID-19 pandemic’s effects on the health and availability of our workforce, as well as those of the third parties on which we rely, could have an adverse effect on our business. If members of our management and other key personnel in critical functions across our organization are unable to perform their duties or have limited availability due to COVID-19, we may not be able to execute on our business strategy and our operations may be adversely affected. Additionally, disruptions in public and private infrastructure, including transportation and supply chains, have adversely affected, and continue to adversely affect, the efficiency of our business operations. Also, the transition of the majority of our workforce to a remote work environment in response to COVID-19, as well as that of our third-party service providers, have exacerbated certain risks to our business, including, but not limited to, those associated with an increased demand for information technology resources, increased risk of cybersecurity attacks (including social engineering attacks), and increased risk of unauthorized dissemination of sensitive personal information or our proprietary or confidential information. As the pandemic continues to progress, we have observed an increase in cybersecurity incidents, predominantly ransomware and social engineering attacks, experienced by our third-party service providers. Further, government entities have also been the subject of cyberattacks. The EMA disclosed in December 2020 that it had been the subject of a cyberattack that targeted and accessed third-party documents relating to regulatory submissions, and that such documents were published on the internet (some of which were manipulated prior to publication). Such third-party and governmental incidents have created the risk of the loss of availability and/or control of information (including information related to our clinical trials) important to the operation of our business. See A breakdown, cyberattack or information security breach could compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation. In the future, as the pandemic progresses and afterwards, we may experience significant adverse effects on our commercial and clinical manufacturing activities, our operations, and our cybersecurity, and our suppliers and vendors may also experience significant disruptions to their activities and operations on which we depend, as a result of these cybersecurity incidents.geographies.

Federal, state and local, and international governmental policies and initiatives designed to reduce the transmission of COVID-19 also have resulted in the cancellation or delay of diagnostic, elective, specialty and other procedures and appointments to avoid non-essential patient exposure to medical environments and potential infection with COVID-19 and to focus limited resources and personnel capacity toward the treatment of COVID-19. For example, an NPR/Harvard poll in 2021 found that, with hospitals crowded from COVID-19, one in five U.S. households had to delay care for serious illnesses. These measures and challenges will likely continue to varying degrees ~~for the duration of the pandemic~~ and have significantly reduced patient access to, and administration of, certain of our drugs. For example, Prolia® ~~is a product requiring~~ requires administration by a healthcare provider in doctors’ offices or other healthcare settings that are affected by COVID-19. The U.S. label for Prolia® instructs healthcare professionals who discontinue Prolia® to transition the patient to an alternative antiresorptive, including oral treatments that do not require administration by a healthcare provider. Further, as a result of COVID-19, oncology patients, in consultation with their doctors, may be selecting therapies that are less immunosuppressive ~~therapies~~ or therapies that do not require administration in a hospital setting, potentially adversely affecting sales of certain of our products. Also, new patients have been, and are expected to continue to be, less likely to be diagnosed and/or to start therapeutics during the ~~pandemic. Once~~pandemic, and these effects, together with the lower treatment rates during the pandemic, ~~subsides,~~have had, and are expected to continue to have, a cumulative negative effect on the commercial performance of our business. The decrease in diagnoses over the course of the pandemic has suppressed the volume of new patients starting treatment, which we expect to continue to impact our business. As COVID-19 infection rates ebb and flow, we anticipate there ~~will~~could be ~~a substantial backlog~~periodic backlogs of patients seeking appointments with physicians relating to a variety of medical conditions, and as a result, patients seeking treatment with certain of our products may have to navigate ~~limited~~lower provider capacity, and this ~~limited~~lower provider capacity could have a continued adverse effect on our ~~sales following the opening up of various geographies and/or the end of the pandemic.~~sales. Further, the effects of the COVID-19 pandemic may result in long-term shifts in preferences among healthcare professionals and patients toward treatments that do not require administration by healthcare professionals or visits to medical facilities.

The legislative and regulatory environment governing our businesses is dynamic and changing frequently in response to COVID-19. For example, the COVID-19 pandemic has resulted in increased interest in compulsory licenses, march-in rights or other governmental interventions, both in the United States and internationally, related to the procurement of drugs, such as the WHO’s COVID-19 Technology Access Pool initiative, which provides an approach for sharing all intellectual property, information and clinical trial data necessary to enable generic drug manufacturing. ~~See Our intellectual property positions may be challenged, invalidated or circumvented, or we may fail to prevail in current and future intellectual property litigation~~. Further, the challenges of the pandemic have resulted in the exploration of signification legislation to address the need to supply medicines to address COVID-19. Pursuant to the declaration of a national emergency in the United States in March 2020 under the Stafford Act, state and local governments may request access to discounted pricing for certain items related to the COVID-19 response. The Coronavirus Aid, Relief and Economic Security (CARES) Act implements initiatives to provide advanced payments from Medicare to healthcare providers, clinics and physicians and to require Medicare plans to provide up to a 90-day supply of Part D drugs. However, despite such initiatives and government support, there may be adverse effects on the timing and collectability of our customer receivables as a result of the COVID-19 pandemic. See ~~Concentration of sales at certain of our wholesaler distributors and at one free-standing dialysis clinic business and consolidation of private payers may negatively affect our business.~~ The COVID-19 pandemic has also resulted in a significant increase in unemployment and underemployment which may continue after the pandemic. Such a significant increase in unemployment or other disruptions in the labor market have led to a substantial reduction in disposable income and, in the U.S., access to healthcare insurance, including reductions in the commercially insured population that has led to growth (and is expected to continue to lead to growth) in Medicaid enrollment, which has adversely affected our product sales. See ~~Global economic conditions may negatively affect us and may magnify certain risks that affect our business~~. Such reduction in healthcare insurance could be compounded by any full or partial repeal of the ACA by the U.S. Supreme Court. Further, globally, the substantial pressures placed on governmental and payor budgets as a result of the COVID-19 pandemic and the projected governmental budget shortfalls caused by significantly reduced economic activity during and potentially after the COVID-19 pandemic, together with the long-term impact from the pressures on healthcare systems, may result in greater and continued downward price pressure on biopharmaceutical products and increased intensity of stakeholder negotiations across the biopharmaceutical value chain. See ~~Our sales depend on coverage and reimbursement from third-party payers, and pricing and reimbursement pressures may affect our profitability.~~

As the pandemic continues, and if conditions worsen or if the duration of the pandemic extends significantly, we expect to experience additional adverse effects on our development, operational and commercial activities, customer purchases and our collections of accounts receivable. It ~~is unclear which adverse effects may be material, and it~~ remains uncertain the degree to which these adverse effects would impact our future operational and commercial activities, customer purchases and our collections ~~even if~~as conditions begin to improve. There was a resurgence in COVID-19 infections in numerous jurisdictions in ~~the autumn of 2020 and winter of 2020-2021,~~2022, resulting in the reinstatement of stricter restrictions and shutdowns in a number of ~~jurisdictions.~~jurisdictions, including in the United States, Europe and Asia Pacific regions. It is expected that the pandemic will continue to ebb and flow, with different jurisdictions having higher levels of infections than others over the course of the pandemic. ~~In addition~~New variants of the SARS-CoV-2 virus have emerged, including the delta and omicron variants and its subvariants, and have been shown to ~~existing travel restrictions, jurisdictions~~be present in many geographies and appear to spread more easily and quickly than other variants. Further, although some studies suggest that antibodies generated with currently authorized vaccines may be effective against these variants, it remains uncertain whether currently available vaccines will retain their efficacy against future variants of the virus. Further, even while vaccine booster shots are available for certain patients, persistent vaccine hesitancy may result in under-vaccinated populations which may prolong the duration of the COVID-19 pandemic and continue to disrupt the availability of healthcare services to the patients we serve. Jurisdictions may implement, continue or reinstate border closures, impose or reimpose prolonged quarantines and further restrict travel and business ~~activity, which~~activity. These measures could significantly affect our ability to support our operations and customers and the ability of our employees to get to their workplaces to discover, study, develop and produce our product candidates and products, disrupt the movement of our products through the supply chain, and further prevent or discourage patients from participating in our clinical trials, seeking healthcare services and the administration of certain of our products. The increased availability of remote working arrangements in response to the COVID-19 pandemic has expanded the pool of companies that can compete for our employees and employment candidates. Further, in connection with the global outbreak and spread of COVID-19 and in an effort to increase the wider availability of needed medical products, we or our suppliers may elect to, or governments may require us or our suppliers to, allocate manufacturing capacity (for example pursuant to the U.S. Defense Production Act) in a way that adversely affects our regular operations, customer relationships and financial results. In the ~~U.S.,~~United States, on January 21, 2021, President Biden issued an Executive Order instructing federal agencies to use all available legal authorities, including the Defense Production Act, to improve current and future pandemic response and biological threat preparedness. The rapid reallocation of resources for the treatment and prevention of COVID-19 ~~including~~(including the production of COVID-19 ~~vaccinations~~vaccines or related therapies, such as our agreement to contribute to the production of ~~one of Lilly’s potential~~ COVID-19 antibody therapies for Lilly) and/or disruptions and shortages in the global supply chain caused by the pandemic, could also result in increased competition for, or reduced availability of, materials or components used in the development, manufacturing, distribution or ~~distribution~~administration of our products. For example, during the second quarter of 2021, an industry-wide shortage of certain lab kit supplies necessary for some activities that support our

clinical trials has developed that we are actively monitoring and managing. We have also experienced challenges in obtaining certain COVID-19-related supplies, including COVID-19 antigen rapid test kits for our staff, as a result of high demand and limited supplies during the omicron variant surge. In addition, unpredictable increases in demand for certain of our products could exceed our capacity to meet such demand, which could adversely affect our financial results and customer relationships.

The COVID-19 pandemic and the volatile global economic conditions stemming from it may precipitate or amplify the other risks described in this “Risk Factors” section, which could materially adversely affect our business, operations and financial ~~conditions~~condition and results. For example, if a natural disaster or other potentially disruptive event occurs concurrently with the COVID-19 pandemic, such disaster or event could deplete our inventory levels and we could experience a disruption to our manufacturing or ability to supply our products. Further, the global pandemic has exacerbated geopolitical tensions, and some countries, such as China, may be especially vulnerable to such dynamics. If relations between the United States and China or other governments deteriorates, our business and investments in China or other such markets may also be adversely affected. See ~~Our sales and operations are subject to the risks of doing business internationally, including in emerging markets.~~

The rapid development and fluidity of the pandemic ~~preclude~~precludes any prediction as to the ultimate effect of COVID-19 on us. The duration of the measures being taken by the authorities to mitigate against the spread of COVID-19 (including the distribution and/or availability of ~~vaccines)~~vaccines and boosters), and the extent to which such measures are effective, if at all, remain highly uncertain. The magnitude and degree of COVID-19’s adverse effect on our business (including our product development, product sales, operating results and resulting cash flows) and financial condition will be driven by the severity and duration of the pandemic, the pandemic’s effect on the United States and global economies and the timing, scope and effectiveness of federal, state, local and international governmental responses to the pandemic. If mitigation of the ~~spread continues at or near its current trajectory or mitigation~~pandemic continues to require ~~similar levels of~~further shelter-in-place and ~~shut-down~~shutdown orders and/or restrictions on individual and/or group conduct, any adverse effects of the COVID-19 pandemic will likely grow and could be enduring, and our business and financial position could be materially adversely affected.

A breakdown of our information technology systems, cyberattack or information security breach could compromise the confidentiality, integrity and availability of our information technology systems, network-connected control systems and/or our data, interrupt the operation of our business and/or affect our reputation.

To achieve our business objectives, we rely on sophisticated information technology systems, including software, mobile applications, cloud services and network-connected control systems, some of which are managed, hosted, provided or serviced by third parties. Internal or external events that compromise the confidentiality, integrity and availability of our systems and data may significantly interrupt the operation of our business, result in significant costs and/or adversely affect our reputation.

Our information technology systems are highly integrated into our business, including our R&D efforts, our clinical and commercial manufacturing processes and our product sales and distribution processes. Further, as the majority of our employees ~~are working~~work remotely for some portion of their jobs in our hybrid work environment, our reliance on our and third-party information technology systems has increased substantially and is expected to continue to increase. The complexity and interconnected nature of our systems makes them potentially vulnerable to breakdown or other service interruptions. Upgrades or changes to our systems or the software that we use may result in the introduction of new cybersecurity vulnerabilities and risks. In 2022 we identified a number of security vulnerabilities introduced into our information systems as a result of flaws that we subsequently identified in software that we purchased and installed, and these flaws required that we apply emergency patches to certain of our systems. While we did not experience any significant adverse effects as a result of these vulnerabilities, there can be no assurance that we will timely identify and address any future vulnerabilities. Our systems are also subject to frequent perimeter network reconnaissance and scanning, phishing and other cyberattacks. As the cyber-threat landscape evolves, these attacks are growing in frequency, sophistication and intensity, and are becoming increasingly difficult to detect. Such attacks could include the use of harmful and virulent malware, including ransomware or other denials of service, that can be deployed through various means, including the software supply chain, e-mail, malicious websites and/or the use of social engineering. We have also experienced denial of service attacks against our network, and although such attacks did not succeed, there can be no assurance that our efforts to guard against the wide and growing variety of potential attack techniques will be successful in the future. Attacks such as those experienced by governmental entities (including those that approve and/or regulate our products, such as the EMA) and other multi-national companies, including some of our peers, could leave us unable to utilize key business systems or access or protect important data and could have a material adverse effect on our ability to operate our business, including developing, gaining regulatory approval for, manufacturing, selling and/or distributing our products. For example, in 2017, a pharmaceutical company experienced a cyberattack involving virulent malware that significantly disrupted its operations, including its research and sales operations and the production of some of its medicines and vaccines. As a result of the cyberattack, its orders and sales for certain products in certain markets were negatively affected. In ~~December~~late 2020, SolarWinds Corporation, a leading provider of software for monitoring and managing information technology infrastructure, disclosed that it had suffered a cybersecurity incident whereby attackers had inserted malicious code into legitimate software updates for its products that were installed by myriad private and government customers, enabling the attackers to access a backdoor to such systems. ~~See~~ ~~The COVID-19 pandemic, and the public and governmental effort~~In 2022, Okta, Inc., a provider of software that helps companies manage user authentication, disclosed that several hundred of its corporate customers were vulnerable to ~~mitigate against the spread of the disease,~~a security breach that allowed

attackers to access Okta’s internal network. Although this breach did not have ~~had, and are expected to continue to have, an adverse~~a significant effect ~~and may have~~on our business, there can be no assurance that a similar future breach would not result in a material adverse effect on our ~~clinical trials, operations, supply chains, distribution systems, product development, product sales,~~ business ~~and~~or results of ~~operations~~ ~~for a discussion of the cyberattack on the EMA.~~operations.

Our systems also contain and utilize a high volume of sensitive data, including intellectual property, trade secrets, financial information, regulatory information, strategic plans, sales trends and forecasts, litigation materials and/or personal information belonging to us, our staff, our patients, customers and/or other parties. In some cases, we utilize third-party service providers to process, store, manage or transmit such data, which may increase our risk. Intentional or inadvertent data privacy or security breaches (including cyberattacks) resulting from attacks or lapses by employees, service providers (including providers of information technology-specific services), business partners, nation states (including groups associated with or supported by foreign intelligence agencies), organized crime organizations, “hacktivists” or others, create risks that our sensitive data may be exposed to unauthorized persons, our competitors or the public. System vulnerabilities and/or cybersecurity breaches experienced by our third-party service providers have constituted a substantial share of the information security risks that have affected us. For example, in the first half of 2021, a supplier experienced a data breach in which an unauthorized third party acquired access to certain information provided to the supplier in the course of its provision of services to us, including business documents and certain personally identifiable patient information (not including social security or other financial or health insurance information). As required, we promptly notified the applicable state attorneys general and the individuals whose personally identifiable information was affected of this data breach at the supplier. In the third quarter of 2022, another service provider experienced a similar cybersecurity breach in which an attacker exfiltrated certain data (including non-significant Amgen data) from the service provider’s systems. Although these supplier data breaches have not resulted in material adverse effects on our business, there can be no assurance that a similar future cybersecurity incident would not result in a material adverse effect on our business or results of operations. Further, the timeliness of our awareness of a cybersecurity incident affects our ability to respond to and work to mitigate the severity of such events. For example, in 2020 and 2022, two of our vendors experienced cyberattacks and each initially reported to us that neither event involved our data. However, upon further investigation, they each subsequently informed us that the attackers had accessed limited, non-significant Amgen information. Although neither of these breaches had a significant adverse effect on our business, in the future we may again not receive timely reporting of cybersecurity events and such events could have a material adverse effect on our business.

Cyberattackers are also increasingly exploiting vulnerabilities in commercially available software from shared or open-source code. We rely on third party commercial software that may have such vulnerabilities, but as use of open-source code is frequently not disclosed, our ability to fully assess this risk to our systems is limited. For example, in December 2021, a remote code execution vulnerability was discovered in a widely used software library that is used in a variety of commercially available software and services. Although this vulnerability has not resulted in any significant adverse effects on us, there can be no assurances that a similar future vulnerability in the software and services that we use would not result in a material adverse effect on our business or results of operations.

Domestic and global government regulators, our business partners, suppliers with whom we do business, companies that provide us or our partners with business services and companies we have acquired or may acquire ~~may~~ face similar risks, and security breaches of their systems or service outages could adversely affect our security, leave us without access to important systems, products, raw materials, components, services or information or expose our confidential ~~data.~~data or sensitive personal information. For example, in 2019, two vendors that perform testing and analytical services that we use in developing and manufacturing our products ~~have~~ experienced cyberattacks, and in April and September of 2020, vendors that provide us with information technology services and clinical data services, respectively, each experienced ransomware attacks. ~~Each~~Although there was no breach of our systems, each of these incidents required us to disconnect our systems from those vendors’ systems. While we were able to reconnect our systems following restoration of these ~~vendor’s~~vendors’ capabilities without significantly affecting product availability, a more extended service outage affecting these or other vendors, particularly where such vendor is the single source from which we obtain the services, could have a material adverse effect on our business or results of operations. In addition, we distribute our products in the United States primarily through three pharmaceutical wholesalers, and a security breach that impairs the distribution operations of our wholesalers could significantly impair our ability to deliver our products to healthcare providers and patients.

Although we have experienced system breakdowns, attacks and information security breaches, we do not believe such breakdowns, attacks and breaches have had a material adverse effect on our business or results of operations. We continue to invest in the monitoring, protection and resilience of our critical and/or sensitive data and systems. However, there can be no assurances that our efforts will detect, prevent or fully recover systems or data from all breakdowns, service interruptions, attacks and/or breaches of our systems that could adversely affect our business and operations and/or result in the loss or exposure of critical, proprietary, private, confidential or otherwise sensitive data, which could result in material financial, legal, business or reputational harm to us or negatively affect our stock price. While we maintain cyber-liability insurance, our insurance is not sufficient to cover us against all losses that could potentially result from a service interruption, breach of our systems or loss of our critical or sensitive data.

We are also subject to various laws and regulations globally regarding privacy and data protection, including laws and regulations relating to the collection, storage, handling, use, disclosure, transfer and security of personal data. The legislative and regulatory environment regarding privacy and data protection is continuously evolving and developing and the subject of significant attention globally. For example, we are subject to the EU’s GDPR, which became effective in May 2018, and the ~~California Consumer Privacy Act of 2018,~~CCPA, which became effective in January 2020, both of which provide for substantial penalties for ~~non-compliance.~~noncompliance. The CCPA was amended in late 2020, to create the California Privacy Rights Act to create opt in requirements for the use of sensitive personal data and the formation of a new dedicated agency for the enforcement of the law, the California Privacy Protection Agency. Virginia, Colorado, Utah and Connecticut have all subsequently passed similar consumer privacy laws, which went into effect in Virginia as of January 1, 2023, and will go into effect in Colorado, Utah and Connecticut later in 2023. Other jurisdictions where we operate have ~~enacted~~passed, or ~~proposed~~continue to propose, similar legislation and/or regulations. For example, in China, the Personal Information Protection Law and the Data Security Law, which regulate data processing activities associated with personal and nonpersonal data, are in effect and build upon the existing Cybersecurity Law. Failure to comply with these current and future laws could result in significant penalties and reputational harm and could have a material adverse effect on our business and results of operations.

Our sales and operations are subject to the risks of doing business internationally, including in emerging ~~markets.~~markets.

As we continue our expansion efforts in emerging markets around the world, through acquisitions and ~~licensing~~licensing transactions as well as through the development and introduction, both independently and through collaborations such as our collaboration with BeiGene, of our products in new markets, we face numerous risks to our business. There is no guarantee that our efforts and strategies to expand sales in emerging markets will succeed. Our international business, including in China and emerging market countries, may be especially vulnerable to periods of global and local political, legal, regulatory and financial instability, including issues of geopolitical relations, the imposition of international sanctions in response to certain state actions and/or sovereign debt issues. Further, in 2022 and continuing through early 2023, the Asia Pacific region also experienced a surge of COVID-19 infections. While one country in the region initially responded to the surge by activating strict containment measures, in late 2022 that country abruptly reversed those measures, resulting in a significant COVID-19 outbreak, causing issues such as lack of capacity at hospitals that could lead to a local health emergencies. If relations between the United States and other governments deteriorate, our business and investments in such markets may also be adversely affected. We may also be required to increase our reliance on third-party agents and unfamiliar operations and arrangements including those previously utilized by companies we partner with or acquire in emerging markets. See We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications. Our expansion efforts in China and emerging markets around the world isare dependent upon the establishment of an environment that is predictable, navigable and supportive of biopharmaceutical innovation, sustained access for our products and ~~limited~~predictable pricing controls. For example, China continues to strengthen regulations on the collection, use and transmission of Chinese human genetic resources, and has expanded regulations on the conduct of biotechnology R&D activities in China. ~~Our~~Between 2020 and 2022, we experienced delays in our applications to the Human Genetic Resources Administration of China ~~(HGRAC) seeking~~that sought approval to conduct clinical trials in ~~China are delayed pending further guidance from HGRAC.~~China. Our international operations and business may also be subject to less protective intellectual property or other applicable laws, diverse data privacy and protection requirements, changing tax laws and tariffs, trade restrictions or other barriers designed to protect industry in the home country against foreign competition, far-reaching antibribery and anticorruption laws and regulations and/or evolving legal and regulatory environments.

33In response to the ongoing armed conflict in Ukraine, the U.S. government, numerous state governments, the EU and other countries in which we conduct business have imposed a wide range of economic sanctions that restrict commerce and business dealings with Russia, certain regions of Ukraine and certain entities and individuals. This conflict may also precipitate or amplify the other risks described herein, including risks relating to cybersecurity, global economic conditions, clinical trials and supply chains, which could adversely affect our business, operations and financial condition and results.

As we expand internationally, we are subject to fluctuations in foreign currency exchange rates relative to the U.S. dollar. While we have a program in place that is designed to reduce our exposure to foreign currency exchange rate fluctuations through foreign currency hedging arrangements, our hedging efforts do not completely offset the effect of these fluctuations on our revenues and earnings. In addition, we have a number of financial instruments referencing the London Interbank Offered Rate (LIBOR). On July 27, 2017, the U.K Financial Conduct Authority, which regulates LIBOR, announced that it will no longer require banks to submit rates for the calculation of LIBOR to the LIBOR administrator after 2021, and it is anticipated that LIBOR will be phased out and replaced by 2023. In March 2020, the Financial Accounting Standards Board issued a new accounting standard to ease the financial burdens of the expected market transition from LIBOR and other interbank offered rates to alternative reference rates. While various replacement reference rates have been proposed, an alternative reference rate to LIBOR has not yet been widely adopted, and the specific mechanisms to replace LIBOR in our existing LIBOR-linked financial instruments have not been finalized. As such, the replacement of LIBOR could have an adverse effect on the market for, or value of, our LIBOR-linked financial instruments. See Part IV, Note 1, Summary of significant accounting policies—Recent accounting pronouncements. We are also subject to the economic and political uncertainties stemming from the United Kingdom’s exit from the EU, commonly referred to as “Brexit,” which occurred on January 31, 2020. While our manufacturing and packaging activities take place largely outside the United Kingdom, minimizing the need to make costly and significant changes to those operations, we have nevertheless been working to put in place contingency plans to attempt to mitigate the effects of Brexit on us. Overall, the legal and operational challenges of our international business operations, along with government controls, the challenges of attracting and retaining qualified personnel and obtaining and/or maintaining necessary regulatory or pricing approvals of our products, may result in material adverse effects on our international product sales, business and results of operations.

RISKS RELATED TO GOVERNMENT REGULATIONS AND THIRD-PARTY POLICIES

Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability.

Sales of our products depend on the availability and extent of coverage and reimbursement from third-party payers, including government healthcare programs and private insurance plans. Governments and private payers continue to pursue initiatives to manage drug utilization and contain costs. ~~These payers~~Further, pressures on healthcare budgets from the pandemic, the economic downturn and inflation continue and are likely to increase across the markets we serve. Payers are increasingly focused on ~~the effectiveness, benefits~~costs, which have resulted, and ~~costs of similar treatments, which could~~are expected to continue to result, in lower reimbursement rates for our products or narrower populations for ~~whom~~which payers will reimburse. Continued intense public scrutiny of the price of drugs and other healthcare costs, together with payer dynamics, have limited, and are likely to continue to limit, our ability to set or adjust the price of our products based on their value, which ~~could~~can have a material adverse effect on our business. In the United States, particularly over the past few years, a number of legislative and regulatory proposals have been introduced ~~in an~~and/or signed into law that attempt to lower drug prices. These include ~~proposals~~legislation promulgated by the IRA that ~~would allow~~enables the U.S. government to ~~negotiate~~set prices for certain drugs in Medicare, redesigns Medicare Part D benefits to shift a greater portion of the costs to manufacturers and enables the U.S. government to impose penalties if drug ~~price directly, limit drug reimbursement based on~~ prices ~~abroad or permit importation of drugs from Canada. Proposals~~are increased at a rate faster than inflation. Additional proposals focused on drug pricing ~~are likely to~~ continue to be ~~proposed~~debated, and ~~may~~additional executive orders focused on drug pricing and competition are likely to be adopted and implemented in some form.

~~—Changing U.S. federal coverage~~ Government actions or ballot initiatives at the state level also represent a highly active area of policymaking and experimentation, including pursuit of proposals that limit drug reimbursement ~~policies and practices have affected and may continue to affect access to, pricing and sales of our products~~

~~A substantial portion of our U.S. business relies on reimbursement from federal government healthcare~~under state run Medicaid programs and commercial insurance plans regulated by federal and state governments. See Item 1. Business—Reimbursement. Our business has been and will continue to be affected by legislative actions changing U.S. federal reimbursement policy. Since late 2018, Congressional focus on drug pricing has increased, placing our industry under greater Congressional scrutiny. For example, in early 2019, the chair of the House Oversight and Reform Committee sent letters to twelve different biopharmaceutical manufacturers, including Amgen, seeking documents and detailed information about such companies’ drug pricing practices. Subsequently, in the fall of 2020, the House Oversight and Reform Committee released staff reports and held hearings with executives from six biopharmaceutical manufacturers, including Amgen, about their companies’ drug pricing practices. Also, between 2019 and 2020, a number of other Congressional committees held hearings and evaluated proposed legislation on drug-pricing and payment policy. For example, in 2019, the Senate Finance Committee advanced a bill that would, among other things, penalize pharmaceutical manufacturers for raising prices on drugs covered by Medicare Parts B and/or D faster than the rate of inflation, cap out-of-pocket expenses for Medicare Part D beneficiaries, and require higher/additional manufacturer discounts in Medicare Part D. Additionally, in late 2019, a drug-pricing bill, H.R. 3, passed the House of Representatives, which would, among other things, enable direct price negotiations by the federal government on certain drugs (with the maximum price paid by Medicare capped by prices derived from an international index), includes a penalty for failing to reach agreement with the government, and requires that manufacturers offer these negotiated prices to other payers. We expect H.R. 3, or some similar proposed legislation, to be debated by Congress this year. Additional legislative or regulatory proposals have been introduced by members of Congress and the prior Administration that, if enacted and implemented in whole or in part, could also affect access to and sales of our products, including, but not limited to, proposals to allow importation of prescription medications from Canada or other countries and to set Medicare payment rates using international price referencing. Further, in mid-2020, the prior Administration announced a number of Executive Orders intended to reduce the cost of biopharmaceuticals for patients, including a MFN policy for Medicare Parts B and D, under which the HHS was directed to take steps to implement payment models that set Medicare purchase prices based on the lowest price available in economically comparable countries for certain Part B and Part D medicines. In September 2020, in response to the corresponding Executive Order, HHS released a final rule to allow states (or other nonfederal government entities) to submit proposals to the FDA allowing for thereference prices or permitting importation of ~~certain nonbiologic prescription~~ drugs from Canada. ~~Currently, the rule is being challenged by litigation, however, should such litigation~~Such state policies may also eventually be ~~unsuccessful and should the Secretary of HHS authorize state proposals for importation, this rule could allow the importation of Canadian versions of certain of Amgen’s products (including Otezla~~®), that could have a material adverse effect on Amgen’s business. Further, in November 2020, also in response to the corresponding Executive Order, HHS released an interim final rule to implement the MFN pricing approach. If implemented, the MFN rule would set the reimbursement rate for 50 Medicare Part B drugs (including our products, such as Prolia®~~, XGEVA~~®~~, KYPROLIS~~®~~, Neulasta~~®~~, Nplate~~®~~, EPOGEN~~® ~~and Aranesp~~®) equal to the lowest adjusted price for such products of the 22 Organization for Economic Co-operation and Development (OECD) nations. Lawsuits have been filed by certain trade groups challenging the implementation of this MFN rule based on, among other things, procedural defects. Late in 2020, in the case filed by the Biotechnology Industry Organization and others, the U.S. District Court for the Northern District of California issued a preliminary injunction preventing the rule from taking effect nationwide, pending the government’s completion of required administrative procedures. The case was subsequently stayed by the court and the parties were ordered to file a joint status report by April 23, 2021. Another case, filed by the Pharmaceutical Research and Manufacturers of America and others in the U.S. District Court for the District of Maryland, was also stayed. Notwithstanding these stays, the MFN rule’s approach to drug pricing and other similar approaches, remain of interest. Further, despite the change in Administration, we expect continued significant focus on healthcare and similar drug pricing proposals, including proposals similar to the MFN rule, for the foreseeable future.

Our business has been, and is expected to continue to be, affected by changes in U.S. federal reimbursement policy resulting from federal regulations and federal demonstration projects. For example, the previous Administration released a drug pricing blueprint in 2018 which introduced an array of policy ideas intended to increase competition, improve the negotiating power ofadopted at the federal government, reduce drug prices and lower patient out-of-pocket costs with the potential to significantly affect, whether individually or collectively, our industry. Such policy ideas included, but were not limited to, moving coverage and reimbursement for Medicare Part B drugs into Medicare Part D and instituting a competitive acquisition program for Part B drugs in which competing third-party vendors take on the financial risk of acquiring drugs and billing Medicare.level.

Also, over the past three years, federal agencies, including the Centers for Medicare & Medicaid Services (CMS), announced a number of recommendations, policies, proposals and demonstration projects to implement various elements of the drug pricing blueprint. CMS is the federal agency responsible for administering Medicare and overseeing state Medicaid programs and Health Insurance Marketplaces and has substantial power to implement policy changes or demonstration projects that can quickly and significantly affect how drugs, including our products, are covered and reimbursed. CMS issued guidance to allow certain Medicare plans offered by private insurance companies to require that patients receiving Medicare Part B drugs first try a drug preferred by the plan before covering another therapy (Step Therapy) and lowered reimbursement rates for new Medicare Part B drugs. Further, HHS issued a final rule under Medicare Part D revising the regulations under the federal antikickback statute to encourage PBMs to use rebates received from biopharmaceutical manufacturers to reduce patient cost-sharing at the point of sale. Changes to the regulations will be phased-in beginning on March 22, 2021, with all changes effective as of January 1, 2023. However, there are numerous logistical hurdles to overcome before such rule can be effectively implemented and it is unclear how PBMs will change their business practices in response. Furthermore, a trade association representing PBMs recently filed litigation challenging this HHS final rule. Given these uncertainties, it remains unclear when any anticipated benefits to patients will materialize. The incoming Administration also could develop and seek to advance a range of policy proposals that could impact U.S. federal reimbursement policy for drugs and biologics.

CMS policy changes and demonstration projects to test new care, delivery and payment models can significantly affect how drugs, including our products, are covered and reimbursed. In end-stage renal disease (ESRD), CMS uses bundled payment rates. Between 2018 and 2020, Sensipar® ~~and Parsabiv~~®, our calcimimetics that are used in dialysis clinics, were eligible for temporary drug add-on payment adjustments (TDAPA) to the bundled rate. In November 2020, CMS released its final rule ending the TDAPA for calcimimetics and adjusting ESRD Prospective Payment System bundled rates on January 1, 2021 by $9.93 per dialysis treatment for calcimimetics, and we expect the sales of our calcimimetics to be materially adversely affected by this rule change. Additionally, CMS created a new mandatory payment model effective January 1, 2021 focused on encouraging greater use of home dialysis and kidney transplants for ESRD patients that could result in changes to treatment of dialysis patients, including reduction of the use of our ESAs. Further, back in November 2019, CMS announced additional voluntary payment models for nephrologists and dialysis facility partners that also seek to encourage home dialysis and preemptive transplantation through increased risk sharing, but due to COVID-19, the start date of such programs has been pushed back to April 1, 2021. CMS has also solicited suggestions regarding other potential care models. In 2016, CMS initiated the Oncology Care Model demonstration, which provides participating physician practices with performance-based financial incentives that aim to manage or reduce Medicare costs without negatively affecting the efficacy of care, that has been extended by one year (to 2022) due to COVID-19. We believe the Oncology Care Model has reduced utilization of certain of our oncology products by participating physician practices and expect it to continue to do so in the future. Additionally, in late 2019, CMS announced a request for information on the Oncology Care First model, a new voluntary model that builds on the Oncology Care Model. CMS recently finalized a rule that, starting January 1, 2023, unless a manufacturer can ensure that the full amount of manufacturer patient assistance programs is passed on to the patient, such amount will be treated as a price reduction that will be taken into account when reporting our Best Price and/or Average Manufacturer Price (AMP). Given the use by PBMs and insurers of copay accumulator adjustment programs to apply such patient assistance for the benefit of such companies and not to defray costs to patients, it could be difficult to impossible for manufacturers to ensure that the full value of such amounts is being passed on to the patient. This new policy, if implemented, would have significant implications for our ability to offer copay assistance programs.

~~In this dynamic environment, we~~ are unable to predict which or how many ~~federal~~ policy, ~~legislative,~~ regulatory, ~~executive~~administrative or ~~administrative~~legislative changes may ultimately be, or effectively estimate the consequences to our business if, enacted and implemented. However, to the extent that ~~these or other federal government initiatives~~payer actions further decrease or modify the coverage or reimbursement available for our products, require that we pay increased rebates or shift other costs to us, limit or affect our decisions regarding the pricing of or otherwise reduce the use of our ~~U.S.~~ products, ~~or limit our ability to offer co-pay payment assistance to commercial patients,~~ such actions could have a material adverse effect on our business and results of operations.

—Changing U.S. federal coverage and reimbursement policies and practices have affected and are likely to continue to affect access to, pricing of and sales of our products

A substantial portion of our U.S. business relies on reimbursement from federal government healthcare programs and commercial insurance plans regulated by federal and state governments. See Part I, Item 1. Business—Reimbursement. Our business has been and will continue to be affected by legislative actions changing U.S. federal reimbursement policy. For example, in August 2022, the IRA was enacted and includes provisions requiring that: (1) beginning in 2026, mandatory price setting be introduced in Medicare for certain drugs paid for under Parts B and D, whereby manufacturers must accept a price established by the government or face penalties on all U.S. sales (starting with 10 drugs in 2026, adding 15 in 2027 and 2028, and adding 20 in 2029 and subsequent years such that by 2031 approximately 100 drugs could be subject to such set prices); (2) starting in 2024, Medicare Part D be redesigned to cap beneficiary out-of-pocket costs and, beginning January 1, 2025, Federal reinsurance be reduced in the catastrophic phase (resulting in a shift and increase of such costs to Part D plans and manufacturers, including by requiring manufacturer discounts on certain drugs); and (3) beginning October 1, 2022, manufacturers will owe rebates on drugs reimbursed under Medicare Part D if price increases outpace inflation, and beginning January 1, 2023, will owe rebates on drugs reimbursed under Medicare Part B if price increases outpace inflation. The IRA’s drug pricing controls and Medicare redesign is likely to have a material adverse effect on our sales (particularly for our products that are more substantially reliant on Medicare reimbursement), our business and our results of operations. However, as the degree of impact from this legislation on our business depends on a number of implementation decisions, the extent of the IRA’s impact on our sales and, in turn, our business remains unclear. Further, following the passage of the IRA, the environment remains dynamic, and in October 2022, the Administration issued an Executive Order on Lowering Prescription Drug Costs for Americans that calls for the HHS to issue a report within 90 days on Innovation Center models that would lower drug costs and promote access to innovative drug therapies for Medicare and Medicaid beneficiaries. This Executive Order follows a 2021 Executive Order that included a timeline designed to increase competition in the healthcare sector, including by calling for the FDA to develop prescription drug importation programs and the FTC to apply greater scrutiny of anticompetitive activity. Responses to this order, including by the HHS, which released a report with drug pricing proposals that seek to promote competition, and by the USPTO, which has taken steps to strengthen coordination with the FDA to address impediments to generic drug and biosimilar competition. CMS policy changes and demonstration projects to test new care, delivery and payment models can also significantly affect how drugs, including our products, are covered and reimbursed. In September 2021, HHS released a plan to address drug pricing that included potential future mandatory models that link payment for prescription drugs and biologics to certain factors, including the overall cost of care.

We also face risks ~~relating~~related to the reporting of pricing data that affects ~~the~~ reimbursement of and discounts provided for our products. U.S. government price reporting regulations are complex and may require a biopharmaceutical ~~manufacturer~~manufacturers to update certain previously submitted data. If our submitted pricing data are incorrect, we may become subject to substantial fines and penalties or other government enforcement actions, which could have a material adverse effect on our business and results of operations. In addition, as a result of restating previously reported price data, we ~~also~~ may be required to pay additional rebates and provide additional discounts.

—Changing reimbursement and pricing actions in various states have negatively affected and may continue to negatively affect access to and have affected and may continue to affect sales of our products

At the state level, government actions or ballot initiatives can also affect how our products are covered and reimbursed and/or create additional pressure on our pricing decisions. A number of states have adopted, and many other states are considering, drug importation programs or other new pricing actions, including proposals designed to require biopharmaceutical manufacturers publicly to report proprietary pricing information, limit price increases or place a maximum price ceiling or cap on biopharmaceutical products. Existing and proposed state pricing laws have added complexity to the pricing of drugs and may already be affecting industry pricing decisions. A number of states have adopted, and many other states are considering, drug importation programs or other pricing actions, including proposals designed to require biopharmaceutical manufacturers to report to the state proprietary pricing information or provide advance notice of certain price increases. For example, a California law ~~the constitutionality of which is currently being challenged, purports to require~~requires biopharmaceutical manufacturers to notify health insurers and government health plans at least 60 days before scheduled prescription drug price increases that exceed certain thresholds. Similar laws exist in Oregon and Washington. Additional proposals directed at Medicaid seek to penalize manufacturers for pricing drugs above a certain threshold or limit spending on biopharmaceutical products. States are also seeking to change the way they pay for drugs for patients covered by state programs. California adopted a 2020-21 budget that incorporates international pricing into Medicaid supplemental rebate negotiations and allows its Medicaid program to seek federal approval to extend supplemental rebates to non-Medicaid populations. New York ~~Massachusetts and Ohio have~~has established a Medicaid drug spending ~~caps,~~cap, and ~~additional~~Massachusetts implemented a new review and supplemental rebate negotiation process. Six states (Colorado, Maine, New Hampshire, Maryland, Oregon and Washington) have enacted laws that establish Prescription Drug Affordability Boards (PDABs) to study drug prices and identify drugs that pose affordability challenges, and in three states (Colorado, Maryland and Washington) include authority for the state PDAB to set upper payment limits on certain drugs in state regulated plans. Other states may consider ~~doing so as they face budget deficits from the effects of COVID-19.~~implementing similar policies and laws. Additionally, Colorado, Florida, Maine, New Hampshire, New Mexico and Vermont have enacted laws, and several other states have proposed ~~laws,~~bills, to ~~facilitate the~~implement importation of drugs from Canada. The FDA has met with representatives from Colorado, Florida, Maine and New Mexico to discuss those states’ proposed importation programs, and the FDA may be working towards approving such plans. Other states could adopt similar approaches or could pursue different policy changes in a continuing effort to reduce their costs. Ultimately, as with U.S. federal government actions, existing or future state government actions or ballot initiatives may also have a material adverse effect on our product sales, business and results of operations.

—U.S. commercial payer actions have affected and may continue to affect access to and sales of our products

Payers, including healthcare insurers, PBMs, integrated healthcare delivery systems (vertically-integrated organizations built from ~~the consolidation~~consolidations of healthcare insurers and PBMs) and group purchasing organizations, increasingly seek ways to reduce their costs. With increasing frequency, payers are adopting benefit plan changes that shift a greater proportion of drug costs to patients. Such measures include more limited benefit plan designs, high deductible plans, higher patient ~~copay~~co-pay or coinsurance obligations and more significant limitations on patients’ use of manufacturer commercial ~~copay~~co-pay assistance programs. Further, government regulation of payers may affect these trends. For example, CMS ~~recently~~ finalized a policy for plan years starting on or after January 1, 2021 that ~~could cause~~has caused commercial payers to more widely adopt ~~copay~~co-pay accumulator adjustment ~~programs more widely.~~programs. Payers, including PBMs, have sought, and ~~will likely~~ continue to seek, price discounts or rebates in connection with the placement of our products on their formularies or those they manage, ~~particularly in treatment areas where the payer has taken the position that multiple branded products are therapeutically comparable. Payers~~and to also ~~control costs by imposing~~impose restrictions on access to or usage of our products ~~such~~(such as Step ~~Therapy, or requiring~~Therapy), require that patients receive the payer’s prior authorization before covering the product, and/or ~~that patients use a mail-order pharmacy or a limited network of payer fully-owned mail-order or specialty pharmacies. Payers may also choose~~chosen to exclude certain indications for which our products are ~~approved or even choose to exclude coverage entirely.~~approved. For example, some payers require physicians to demonstrate or document that the patients for whom Repatha® has been prescribed meet ~~payer~~their utilization ~~management~~ criteria, and these requirements have ~~limited,~~served to limit and may continue to limit patient access to Repatha® treatment. In an effort to reduce barriers to access, we reduced the net price of Repatha® by providing greater discounts and rebates to payers ~~including~~(including PBMs that administer Medicare Part D prescription drug ~~plans.~~plans), and in response to a very high percentage of Medicare patients abandoning their Repatha prescriptions rather than paying their co-pay, we introduced a set of new National Drug Codes to make Repatha available at a lower list price. However, affordability of patient out-of-pocket co-pay cost has limited and may continue to limit patient use. ~~For example, in late 2018 and early 2019, in response to a very high percentage of Medicare patients abandoning their Repatha~~® ~~prescriptions rather than pay their co-pay payment, we introduced a set of new National Drug Codes to make Repatha~~® ~~available at a lower list price to attempt to address affordability for patients, particularly those on Medicare and on December 31, 2019, we discontinued the higher list price option for Repatha~~®~~. Despite~~Further, despite these net and list price reductions, some payers have restricted, and may continue to restrict, patient access and may ~~change formulary coverage for Repatha~~®, seek further discounts or rebates or take other actions, such as changing formulary coverage for Repatha, that could reduce our sales of ~~Repatha~~®.Repatha. These factors have limited, and may continue to limit, patient affordability and use, ~~and~~ negatively ~~affect~~affecting Repatha® sales.

Further, significant consolidation in the health insurance industry has resulted in a few large insurers and PBMs, which places greater pressure on pricing and usage negotiations with biopharmaceutical manufacturers, significantly increasing discount and rebate requirements and limiting patient access and usage. For example, in the United States, ~~in 2020,~~as of the beginning of 2023, the top five integrated health plans and PBMs controlled about ~~85%~~92% of all pharmacy prescriptions. ~~The~~ This high degree of

consolidation among insurers and PBMs and other payers, including through integrated healthcare delivery systems and/or with specialty or mail-order pharmacies and pharmacy retailers, has increased the negotiating leverage such entities have over us and other biopharmaceutical manufacturers and has resulted in greater price discounts, rebates and service fees realized by those ~~payers. In 2019 and 2020,~~payers from our business. Each of CVS, ~~and~~ Express Scripts ~~created~~and United Health Group (among the top five integrated health plans and PBMs), each have Rebate Management Organizations that further increase their ~~respective~~ leverage to negotiate deeper discounts. Ultimately, additional discounts, rebates, fees, coverage orchanges, plan changes, restrictions or exclusions imposed by these commercial payers could have a material adverse effect on our product sales, business and results of operations. Policy reforms advanced by Congress or the Administration that refine the role of PBMs in the U.S. marketplace could have downstream implications or consequences for our business and how we interact with these entities. For example, on June 7, 2022, the FTC launched an inquiry into the business practices of PBMs, and the results of such inquiry could have an effect on manufacturer interactions with PBMs, resulting in changes to access for certain medicines. See our —Concentration of sales at certain of our wholesaler distributors and consolidation of private payers may negatively affect our business.

Our business is also affected by policies implemented by private healthcare entities that process Medicare claims, including Medicare Administrative Contractors. For example, in the second quarter of 2022, several Medicare Administrative Contractors issued notice, in contravention of TEZSPIRE’s FDA approved labeling, that TEZSPIRE would be added to their “self-administered drug” exclusion lists. Although the Medicare Administrative Contractors subsequently removed TEZSPIRE from their exclusion lists, these exclusions, if reintroduced and/or implemented, would result in Medicare beneficiaries with severe asthma losing access to TEZSPIRE coverage under Medicare Part B and potentially also under Medicare Advantage.

—Government and commercial payer actions outside the United States have affected and will continue to affect access to and sales of our products

Outside the United States, we expect countries will also continue to take actions to reduce their drug expenditures. See Part I, Item 1. Business—Reimbursement. ~~IRP~~Pressures to decrease drug expenditures may further intensify as the COVID-19 pandemic has strained government budgets and as economic conditions continue to worsen in certain regions, including in Europe where high inflation and the energy crisis relating to the Russia–Ukraine conflict are challenging the economies in that region. International reference pricing has been widely used by many countries outside the United States to control costs based on an external benchmark of a product’s price in other countries. ~~IRP~~International reference pricing policies can change quickly and frequently and may not reflect differences in the burden of disease, indications, market structures or affordability differences across countries or regions. Other expenditure control practices, including but not limited to the use of revenue clawbacks, rebates and percentage caps on price increases, are used in various foreign jurisdictions as well. In addition, countries may refuse to reimburse or may restrict the reimbursed population for a product when their national health technology assessments do not consider a medicine to demonstrate sufficient clinical benefit beyond existing therapies or to meet certain cost effectiveness thresholds. For example, despite the EMA’s approval of Repatha® for the treatment of patients with established atherosclerotic disease, prior to 2020, the reimbursement ~~for~~of Repatha® in France iswas limited to a narrower patient population (such as those with homozygous familial ~~hypercholesterolemia)~~hypercholesterolemia (HoFH)) following a national health technology assessment. ~~While the pricing and reimbursement process in that country remains ongoing, the assessment currently limits our efforts in France to expand Repatha~~® ~~access to the broader patient population covered by the approved label. Some~~Many countries decide on reimbursement between potentially competing products through national or regional tenders that often result in one product receiving most or all of the sales in that country or region. Failure to obtain coverage and reimbursement for our products, a deterioration in their existing coverage and reimbursement or a decline in the timeliness or certainty of payment by payers to physicians and other providers has negatively affected, and may further negatively affect, the ability or willingness of healthcare providers to prescribe our products for their patients and otherwise negatively affect the use of our products or the prices we realize for them. Such changes have had, and could in the future have, a material adverse effect on our product sales, business and results of operations.

Guidelines and recommendations published by various organizations can reduce the use of our products.

Government agencies promulgate regulations and guidelines directly applicable to us and to our products. Professional societies, practice management groups, insurance carriers, physicians’ groups, private health and science foundations and organizations involved in various diseases also publish guidelines and recommendations to healthcare providers, administrators and payers, as well as patient communities. Recommendations by government agencies or other groups and organizations may relate to such matters as usage, dosage, route of administration and use of related therapies. In addition, a growing number of organizations are providing assessments of the value and pricing of biopharmaceutical products, and even organizations whose guidelines have historically been focused on clinical matters have begun to incorporate analyses of the cost effectiveness of various treatments into their treatment guidelines and recommendations. Value assessments may come from private organizations that publish their findings and offer recommendations relating to the products’ reimbursement by government and private payers. Some companies and payers have announced pricing and payment decisions based in part on the assessments of private organizations. In addition, government health technology assessment organizations in many countries make reimbursement recommendations to payers in their jurisdictions based on the clinical effectiveness, cost-effectiveness and service effects of new, emerging and existing medicines and treatments. Such health technology assessment organizations have

recommended, and may in the future recommend, reimbursement for certain of our products for a narrower indication than was approved by applicable regulatory agencies or may recommend against reimbursement entirely. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures have affected, and are likely to continue to affect, our profitability. Such recommendations or guidelines may affect our reputation, and any recommendations or guidelines that result in decreased use, dosage or reimbursement of our products could have a material adverse effect on our product sales, business and results of operations. In addition, the perception by the investment community or stockholders that such recommendations or guidelines will result in decreased use and dosage of our products could adversely affect the market price of our common stock.

The adoption and interpretation of new tax legislation or exposure to additional tax liabilities could affect our profitability.

We are subject to income and other taxes in the United States and other jurisdictions in which we do business. As a result, our provision for income taxes is derived from a combination of applicable tax rates in the various places we operate. Significant judgment is required for determining our provision for income tax.

One or more of our legal entities file income tax returns in the U.S. federal jurisdiction, various U.S. state jurisdictions and certain foreign jurisdictions. Our income tax returns are routinely examined by tax authorities in those jurisdictions. Significant disputes can and have arisen with tax authorities involving issues regarding the ~~United States~~timing and ~~other~~amount of deductions, the use of tax credits and allocations of income and expenses among various tax jurisdictions ~~in which we do business,~~because of differing interpretations of tax laws, regulations and ~~a number of audits are currently underway. Tax~~relevant facts, and such tax authorities ~~including~~(including the ~~Internal Revenue Service (IRS),~~IRS) are becoming more aggressive in their audits and are particularly focused on ~~the allocations of income and expense among tax jurisdictions.~~such matters. In 2017, we received ~~a Revenue Agent Report (RAR)~~an RAR and a modified RAR from the IRS for the years ~~2010, 2011 and~~ 2010–2012, proposing significant adjustments that primarily relate to the allocation of profits between certain of our entities in the United States and the U.S. territory of Puerto Rico. We ~~disagree~~disagreed with the proposed adjustments and calculations and ~~have been pursuing~~pursued resolution with the IRS administrative appeals ~~office. However, we have been~~office but were unable to reach ~~resolution at~~resolution. In July 2021, we filed a petition in the ~~administrative appeals level, and we anticipate~~U.S. Tax Court to contest two duplicate Statutory Notices of Deficiency (Notices) for the years 2010–2012 that we ~~will receive a Notice of Deficiency~~received in May and July 2021 which ~~we would expect~~seek to ~~vigorously contest through~~increase our U.S. taxable income for the ~~judicial process.~~ years 2010–2012.

In ~~addition, in~~ 2020, we received an RAR and a modified RAR from the IRS for the years ~~2013, 2014 and~~ 2013–2015, also proposing significant adjustments that primarily relate to the allocation of profits between certain of our entities in the United States and the U.S. territory of Puerto Rico similar to those proposed for the years ~~2010, 2011 and~~ 2010–2012. We ~~disagree~~disagreed with the ~~2013, 2014 and 2015~~ proposed adjustments and calculations and ~~are pursuing~~pursued resolution with the IRS ~~administrative~~ appeals ~~office. The IRS audit for years 2016, 2017 and 2018 is expected~~office but were unable to ~~start~~reach resolution. In July 2022, we filed a petition in the ~~near term.~~U.S. Tax Court to contest a Notice for the years 2013–2015 that we previously reported receiving in April 2022 that seeks to increase our U.S. taxable income for the years 2013–2015 and asserts penalties.

We firmly believe that the IRS positions set forth in the 2010–2012 and 2013–2015 Notices are without merit. We are contesting the 2010–2012 and 2013–2015 Notices through the judicial process. The cases were consolidated on December 19, 2022.

We are currently also ~~currently~~under examination by the IRS for the years 2016–2018 with respect to issues similar to those for the 2010 through 2015 period. In addition, we are under examination by a number of ~~other~~ state and foreign tax jurisdictions.

Final resolution of these complex tax matters is not likely within the next 12 months. We continue to believe our accrual for income tax liabilities is appropriate based on past experience, interpretations of tax law, application of the tax law to our facts and judgments about potential actions by tax authorities; however, due to the complexity of the provision for income taxes and uncertain resolution of these matters, the ultimate outcome of any tax matters may result in payments substantially greater than amounts accrued and could have a material adverse effect on the results of our operations.

See Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations—Results of Operations, Income Taxes, and Part IV—Note 6, Income taxes, to the Consolidated Financial Statements.

Our provision for income taxes and results of operations in the future could be adversely affected by changes to our operating structure, changes in the mix of income and expenses in countries with differing tax rates, changes in the valuation of deferred tax assets and liabilities and changes in applicable tax laws, regulations or administrative interpretations thereof. The ~~Tax Cuts and Jobs Act (the~~ 2017 Tax ~~Act)~~Act is complex and a large volume of regulations and guidance has been issued and could be subject to different interpretations. We could face audit challenges to our application of the 2017 Tax Act. In addition, there are several upcoming provisions in the 2017 Tax Act, including increases in the tax rates on foreign earnings and export income scheduled to take effect at the end of 2025, that could result in an increase in our effective tax rate.

The ~~new~~ Administration and Congress ~~could make~~continue to discuss changes to existing tax law ~~including~~that could substantially increase the taxes we pay in the United States. Further, the OECD reached an ~~increase in the~~agreement to align countries on a minimum corporate tax rate and an expansion of the taxing rights of market countries. Some individual countries, including those in the EU, have proposed

legislation to implement the global minimum tax ~~rate on~~agreement. In other countries such as the United States, however, the implementation of the OECD agreement remains highly uncertain. If enacted, either by all OECD participants or unilaterally by individual countries, the agreement could result in tax increases or double taxation that could affect our United States or foreign ~~earnings.~~tax liabilities. Changes to existing tax law in the ~~U.S.,~~United States, the U.S. territory of Puerto Rico or other jurisdictions, including ~~efforts by~~ the ~~OECD to align countries on corporate tax matters that would likely~~changes and potential changes discussed above, could result in tax increases where we do business and could have a material adverse effect on the results of our operations.

Our business may be affected by litigation and government investigations.

We and certain of our subsidiaries are involved in legal proceedings. See Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements. Civil and criminal litigation is inherently unpredictable, and the outcome can result in costly verdicts, fines and penalties, exclusion from federal healthcare programs and/or injunctive relief that affect how we operate our business. Defense of litigation claims can be expensive, time consuming and distracting, and it is possible that we could incur judgments or enter into settlements of claims for monetary damages or change the way we operate our business, which could have a material adverse effect on our product sales, business and results of operations. In addition, product liability is a major risk in testing and marketing biotechnology and pharmaceutical products. We may face substantial product liability exposure in human clinical trials and for products we sell after regulatory approval. Product liability claims, regardless of their merits, could be costly and divert management’s attention and could adversely affect our reputation and the demand for our products. We and certain of our subsidiaries have previously been named as defendants in product liability actions for certain of our products.

We are also involved in government investigations that arise in the ordinary course of our business. In recent years, there has been a trend of increasing government investigations and litigations against companies operating in our industry, both in the United States and around the world. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures ~~may~~have affected, and are likely to continue to affect, our profitability. Our business activities outside of the United States are subject to the FCPA and similar antibribery or anticorruption laws, regulations or rules of other countries in which we operate, including the UKU.K. Bribery Act. We cannot ensure that all our employees, agents, contractors, vendors, licensees, partners or collaborators will comply with all applicable laws and regulations. On April 25, 2019, we entered into a settlement agreement with the DOJ and the OIG of the HHS to settle certain allegations relating to our support of independent charitable organizations that provide patients with financial assistance to access their medicines. As a result, we entered into a corporate integrity agreement with the OIG that requires us to maintain a corporate compliance program and to undertake a set of defined corporate integrity obligations for a period of five years. While we expect to fully comply with all of our obligations under the corporate integrity agreement, failure to do so could result in substantial penalties and potential exclusion from government healthcare programs. We may also see new government investigations of or actions against us citing novel theories of recovery. For example, prosecutors are placing greater scrutiny on patient support programs, including commercial copay assistance programs, and further enforcement actions and investigations regarding such programs could limit our ability to provide co-pay assistance to commercial patients. Greater scrutiny has also been placed on sponsorships, speaker programs and other arrangements where healthcare professionals receive remuneration, travel or other value to participate in certain events, and further enforcement actions could limit our ability to participate in such arrangements. Any of these results could have a material adverse effect on our business and results of operations.

RISKS RELATED TO COMPETITION

Our products face substantial competition and our product candidates are also likely to face substantial competition.

We operate in a highly competitive environment. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition. We expect that our products and product candidates will compete with existing drugs, new drugs currently in development, drugs currently approved for other indications that may later be approved for the same indications as those of our products and drugs approved for other indications that are used off-label. Large pharmaceutical companies and generics manufacturers of pharmaceutical products have expanded into, and are expected to continue expanding into, the biotechnology field, and some pharmaceutical companies and generics manufacturers have formed partnerships to pursue biosimilars. With the proliferation of companies pursuing biopharmaceuticals, several of our biosimilar products have entered, and a number of our product candidates may enter, markets with one or more competitors or with competitors soon to arrive. In addition, some of our competitors may have technical, competitive or other advantages over us for the development of technologies and processes or greater experience in particular therapeutic areas, and consolidation among pharmaceutical and biotechnology companies can enhance such advantages. These advantages may make it difficult for us to compete with them successfully to discover, develop and market new products and for our current products to compete with new products or new product indications they may bring to market. As a result, our products have been competing and may continue to compete, and our product candidates may compete, against products or product candidates that offer higher rebates or discounts, lower prices, equivalent or superior efficacy, better safety profiles, easier administration, earlier market availability or other competitive

features. If we are unable to compete effectively, this could reduce our sales, which could have a material adverse effect on our business and results of operations.

Our intellectual property positions may be challenged, invalidated or circumvented, or we may fail to prevail in current and future intellectual property litigation.

Our success depends in part on our ability to obtain and defend patent rights and other intellectual property rights that are important to the commercialization of our products and product candidates. The patent positions of pharmaceutical and biotechnology companies can be highly uncertain and often involve complex legal, scientific and factual questions. Driven by cost pressures, efforts to limit or weaken patent protection for our industry are increasing. For example, the COVID-19 pandemic has resulted in increased interest in compulsory licenses, march-in rights or other governmental interventions, both in the United States and internationally, related to the procurement of ~~drugs.~~drugs, and the World Trade Organization has agreed to a waiver of COVID-19 vaccine intellectual property protections through the Trade-Related Aspects of Intellectual Property Rights waiver process. See The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, manufacturing, supply chains, distribution systems, product development, product sales, business and results of operations. Third parties have challenged and may continue to challenge, invalidate or circumvent our patents and patent applications relating to our products, product candidates and technologies. Challenges to patents may come from potential competitors or from parties other than those who seek to market a potentially-infringing product. In addition, our patent positions might not protect us against competitors with similar products or technologies because competing products or technologies may not infringe our patents. For certain of our product candidates, there are third parties who have patents or pending patent applications that they may claim necessitate payment of a royalty or prevent us from commercializing these product candidates in certain territories. Patent disputes are frequent, costly and can preclude, delay or increase the cost of commercialization of products. We have been in the past, are currently and expect to be in the future, involved in patent litigation. These matters have included, and may in the future include, litigation with manufacturers of products that purport to be biosimilars of certain of our products for patent infringement and for failure to comply with certain provisions of the ~~Biologics Price Competition and Innovation Act of 2009 (BPCIA).~~BPCIA. A determination made by a court, agency or tribunal concerning infringement, validity, enforceability, injunctive or economic remedy, or the right to patent protection, for example, are typically subject to appellate or administrative review. Upon review, such initial determinations may be afforded little or no deference by the reviewing tribunal and may be affirmed, reversed or made the subject of reconsideration through further proceedings. A patent dispute or litigation has not discouraged, and may not in the future discourage, a potential violator from bringing the ~~allegedly-infringing~~allegedly infringing product to market prior to a final resolution of the dispute or litigation. The period from inception until resolution of a patent dispute or litigation is subject to the availability and schedule of the court, agency or tribunal before which the dispute or litigation is pending. We have been, and may in the future be, subject to competition during this period and may not be able to recover fully from the losses, damages and harms we incur from infringement by the competitor product even if we prevail. Moreover, if we lose or settle current or future litigations at certain stages or entirely, we could be subject to competition and/or significant liabilities, be required to enter into third-party licenses for the infringed product or technology or be required to cease using the technology or product in dispute. In addition, we cannot guarantee that such licenses will be available on terms acceptable to us, or at all.

Further, under the ~~Hatch-Waxman~~Hatch–Waxman Act, our products approved by the FDA under the FDCA have been, and may in the future be, the subject of patent litigation with generics competitors before expiry of the five-year period of data exclusivity provided for under the Hatch-Waxman Act and prior to the expiration of the patents listed for the product. Likewise, our innovative biologic products have been, and may in the future be, the subject of patent litigation prior to the expiration of our patents and, with respect to competitors seeking approval as a biosimilar or interchangeable version of our products, prior to the 12-year exclusivity period provided under the BPCIA. In addition, we have faced, and may in the future face, patent litigation involving claims that the biosimilar product candidates we are working to develop infringe the patents of other companies, including those that manufacture, market or sell the applicable reference products or who are developing or have developed other biosimilar versions of such products. Due to the COVID-19 pandemic, there may be delays in ongoing or new patent office or court proceedings in the U.S. or abroad that may delay the outcome of such proceedings. While we have attempted, and expect to continue to attempt, to challenge theAlternatively, patents held by other ~~companies, our efforts may be unsuccessful. Alternatively, such patents~~entities have contributed, and may in the future contribute, to a decision by us to not pursue all of the same labeled indications as are held by these companies. While we have attempted, and expect to continue to attempt, to challenge the patents held by other companies, our efforts may be unsuccessful. For examples of and information related to our patent litigation, see Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements.

Certain of the existing patents on our products have ~~expired.~~expired or will soon expire. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Patents. As our patents expire, competitors are able to legally produce and market similar products or technologies, including biosimilars, which has had, and may continue to have, a material adverse effect on our product sales, business and results of operations. In addition, competitors have been, and may continue to be, able to invalidate, design around or otherwise circumvent our patents and sell competing products.

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We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future.

We currently face competition from biosimilars and generics in most of the territories in which we operate, including ~~Europe and~~ the United States and Europe, and we expect to face increasing biosimilar and/or generics competition this year and beyond. Expiration or successful challenge of applicable patent rights or expiration of an applicable exclusivity period has accelerated such competition, and we expect to face more litigation regarding the validity and/or scope of our patents. Our products have also experienced greater competition from lower cost biosimilars or generics that come to market when branded products that compete with our products lose their own patent protection. To the extent that governments adopt more permissive regulatory approval standards and competitors are able to obtain broader or expedited marketing approval for biosimilars and generics, the rate of increased competition for our products could accelerate.

In the EU, biosimilars are evaluated for marketing authorization pursuant to a set of general and product class-specific guidelines. In addition, in an effort to spur biosimilar utilization and/or increase potential healthcare savings, some EU countries and some Canadian provinces have adopted, or are considering the adoption of, biosimilar uptake measures such as physician prescribing quotas or automatic pharmacy substitution of biosimilars for the corresponding reference products. Some EU countries impose automatic price reductions upon market entry of one or more biosimilar competitors. In September 2022, the EMA and the EU Heads of Medicines’ Agencies (HMA) issued a joint statement providing that biosimilar medicines approved in the EU are “interchangeable” with their reference products and other biosimilars of the same reference product. This EMA-HMA statement could further contribute to the prescribing of biosimilars and to greater competition in Europe. While the degree of competitive effects of biosimilar competition differs between EU countries and between products, in the EU the overall use of biosimilars and the rate at which product sales of innovative products are being affected by biosimilar competition is increasing.

In the United States, the BPCIA authorizes the FDA to approve biosimilars via a separate, abbreviated pathway. See Item 1. Business—Government Regulation—Regulation in the United States—Approval of Biosimilars. ~~The first biosimilar entrant into~~In the ~~U.S. market was Sandoz’s Zarxio~~® ~~(filgrastim-sndz), a biosimilar version of NEUPOGEN~~®~~, in 2015. Since then,~~United States, the FDA has approved ~~additional~~numerous biosimilars, including biosimilar versions of Neulasta,®, EPOGEN® and ENBREL, and a growing number of companies have announced that they are also developing biosimilar versions of our products. ~~Four~~For example, six biosimilar versions of Neulasta® are now ~~marketed~~approved in the United States, and we expect that other biosimilar versions of Neulasta® to may be marketed or receive approval in ~~2021 and beyond.~~the future. Impact to our Neulasta® sales has accelerated as additional competitors have launched. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition. ~~An approved biosimilar version of EPOGEN~~® ~~has also launched in the United States, and we are currently involved in patent litigations with the manufacturers of the approved biosimilar versions of ENBREL.~~ Manufacturers of biosimilars have attempted, and may in the future attempt, to compete with our products by offering lower list prices, greater discounts or rebates, or contracts that offer longer-term pricing or a broader portfolio of other products. Companies pursuing development of biosimilar versions of our products have challenged and may continue to challenge our patents well in advance of the expiration of our material patents. For ~~example, we recently successfully defended our ENBREL patents against a litigation challenge. For~~ examples of and information related to our biosimilars and generics patent litigation, see Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements. See Our intellectual property positions may be challenged, invalidated or circumvented, or we may fail to prevail in current and future intellectual property litigation.

The U.S. biosimilar pathway includes the option for biosimilar products that meet certain criteria to be approved as interchangeable with their reference products. Some companies currently developing or already marketing biosimilars may seek to obtain interchangeable status from the FDA, which could potentially allow pharmacists to substitute those biosimilars for our reference products without prior approval from the prescriber in most ~~states.~~states under state law. The FDA approved the first interchangeable biosimilar in 2021 and has subsequently granted interchangeability designations to three additional biosimilars. In ~~November~~ 2019, the FDA issued draft guidance that provides that comparative immunogenicity studies will not generally be expected for biosimilar and interchangeable insulin products. This ~~may open~~has opened the door for other product-specific guidance development and the removal of the expectation for certain studies, which may contribute to increased biosimilar competition for our innovative products. For example, in August 2022, the FDA designated a monoclonal antibody biosimilar as interchangeable without requiring a switching study to support the interchangeability determination. Further, in September 2022, the FDA indicated that while comparative clinical trials will continue to be a requirement for many biosimilar development programs, the agency is focused on reducing the need for them in the future through a range of statistical, analytical and pharmacologic approaches.

In addition, critics of the 12-year exclusivity period in the biosimilar pathway law will likely continue to seek to shorten the data exclusivity period and/or to encourage the FDA to interpret narrowly the law’s provisions regarding which new products receive data exclusivity. In ~~late~~ 2019, the ~~previous~~ Administration agreed to remove from the United States-Mexico-Canada Agreement a requirement for at least 10 years of data exclusivity for biologic products. Also, the FDA is considering whether subsequent changes to a licensed biologic would be protected by the remainder of the reference product’s original 12-year exclusivity period (a concept known in the generic drug context as “umbrella exclusivity”). If the FDA were to decide that umbrella exclusivity does not apply to biological reference products or were to make other changes to the exclusivity period,

this could expose us to biosimilar competition at an earlier time. There also have been, and may continue to be, legislative and regulatory efforts to promote competition through policies enabling easier generic and biosimilar approval and commercialization, including efforts to lower standards for demonstrating biosimilarity or interchangeability, limit patents that may be litigated and/or patent settlements, implement preferential reimbursement policies for biosimilars and ~~passage of~~pass new laws requiring more disclosure in the FDA’s Orange and Purple Books. For example, in 2021 the FDA sent a letter to the USPTO describing ways to strengthen coordination between the two agencies, offered training to help identify prior art, and seeking USPTO’s views on practices that extend market exclusivities, whether pharmaceutical patent examiners need additional resources, and the effect of post-grant challenges at the Patent Trial and Appeal Board on drug patents. The USPTO responded in July 2022 with a letter to the FDA stating that it is prepared to create formal mechanisms to collaborate with the FDA on patent issues that may affect the timing of generic and biosimilar entry. In January 2023, the USPTO held a joint listening session with the FDA on USPTO-FDA collaboration efforts.

Upon the expiration or loss of patent protection and/or applicable exclusivity for one of our ~~small molecule~~ products, we can lose the majority of revenues for that product in a very short period of time. See Item 1. Business—Marketing, Distribution and Selected Marketed Products—Competition. Additionally, if one of our ~~small molecule~~ products is the subject of an FDA Written Request for pediatric studies and we are unable to adequately complete these studies, we may not obtain the pediatric exclusivity award that extends unexpired regulatory exclusivity for the product (and existing patents for ~~the product~~a small molecule product) by an additional six months. ~~For example,~~

While we are unable to predict the precise effects of biosimilars and generics on our products, we are currently facing and expect to face greater competition in the United States, Europe and elsewhere as a result of ~~the~~biosimilar and generic competition and, in turn, downward pressure on our product ~~already introduced and/or that~~prices and sales. This competition has had, and could ~~further be introduced into the U.S. market,~~increasingly have, a material adverse effect on our product sales, ~~for Sensipar~~®business and results of operations. State laws may also have ~~been adversely affected and could be further materially and adversely affected by competing generics.~~

an impact on our business. For example, California is the first state to have passed legislation, effective on January 1, 2020, against “pay for delay” settlements of patent infringement claims filed by manufacturers of generics or biosimilars where anything of value is given in exchange for settlement. Under this law, such settlement agreements are presumptively anticompetitive. The law may result in prolonged litigation and fewer settlements. Other states, including Connecticut, New York, Illinois and Minnesota, may adopt similar laws or a similar law could be adopted at the federal level.

Concentration of sales at certain of our wholesaler distributors ~~and at one free-standing dialysis clinic business~~ and consolidation of private payers may negatively affect our business.

Certain of our distributors, customers and payers have substantial purchasing leverage, due to the volume of our products they purchase or the number of patient lives for which they provide coverage. The substantial majority of our U.S. product sales is made to three pharmaceutical product wholesaler distributors: McKesson Corporation, AmerisourceBergen ~~McKesson~~Corporation and Cardinal ~~Health.~~Health, Inc. These distributors, in turn, sell our products to their customers, which include physicians or their clinics, dialysis centers, hospitals and pharmacies. ~~One of our products, EPOGEN~~®, is sold primarily to free-standing dialysis clinics. DaVita owns or manages a large number of the outpatient dialysis facilities located in the United States and accounts for approximately 90% of all EPOGEN® ~~sales.~~ Similarly, as discussed above, there has been significant consolidation in the health insurance industry, including that a small number of PBMs now oversee a substantial percentage of total covered lives in the United States. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures ~~may~~have affected, and are likely to continue to affect, our ~~profitability~~profitability. . The three largest PBMs in the United States are now part of major health insurance providers. The growing concentration of purchasing and negotiating power by these entities has, and may continue to, put pressure on our pricing due to their ability to extract price discounts on our products, fees for other services or rebates, negatively affecting our bargaining position, sales and/or profit margins. In addition, decisions by these entities to purchase or cover less or none of our products in favor of ~~competitive~~competing products could have a material adverse effect on our product sales, business and results of operations due to their purchasing volume. Further, if one of our significant wholesale distributors encounters financial or other difficulties and becomes unable or unwilling to pay us all amounts that such distributor owes us on a timely basis, or at all, it could negatively affect our business and results of operations. In addition, if one of our significant wholesale distributors becomes insolvent or otherwise unable to continue its commercial relationship with us in its present form, it could significantly disrupt our business and adversely affect our product sales, our business and results of operations unless suitable alternatives are timely found or lost sales are absorbed by another distributor.

RISKS RELATED TO RESEARCH AND DEVELOPMENT

We may not be able to develop commercial products despite significant investments in R&D.

Amgen invests heavily in R&D. Successful product development in the biotechnology industry is highly uncertain, and very few R&D projects ~~produce commercial~~yield approved and commercially viable products. Product candidates, including biosimilar product candidates, or new indications for existing products (collectively, product candidates) that appear promising in the early phases of development ~~may fail~~have failed to reach the market for a number of reasons, such as:

•the product candidate did not demonstrate acceptable clinical trial results even though it achieved its primary endpoints and/or demonstrated positive preclinical or early clinical trial results, for reasons that could include changes in the standard of care of medicine or expectations of health authorities;

•the product candidate was not effective or not more effective than currently available or potentially competitive therapies in treating a specified condition or illness;

•the product candidate was not cost effective in light of existing or potentially competitive therapeutics;

•the product candidate had harmful side effects in animals or humans;

•the necessary regulatory bodies, such as the FDA or EMA, did not approve the product candidate for an intended use;

•reimbursement for the product candidate is limited despite regulatory approval;

•the product candidate was not economical for us to manufacture and commercialize;

•other parties had or may have had proprietary rights relating to our product candidate, such as patent rights, and did not let us sell it on reasonable terms, or at all;

•we and certain of our licensees, partners, contracted organizations or independent investigators ~~may have~~ failed to effectively conduct clinical development or clinical manufacturing activities;

•the pathway to regulatory approval or reimbursement for product candidates was uncertain or not well-defined;

•the biosimilar product candidate failed to demonstrate the requisite biosimilarity to the applicable reference product, or was otherwise determined by a regulatory authority to not meet applicable standards for approval; and

•a companion diagnostic device that is required with the use of a product candidate is not approved by the necessary regulatory authority.

We have spent considerable time, energy and resources developing our expertise in human genetics and acquiring access to libraries of genetic information with the belief that genetics could meaningfully aid our search for new medicines and help guide our R&D decisions and investments. We have focused our R&D strategy on drug targets validated by genetic or other compelling human evidence. However, product candidates based on genetically validated targets remain subject to the uncertainties of the drug development process and may not reach the market for a number of reasons, including the factors listed above.

A number of our product candidates have failed or been discontinued at various stages in the product development process. For example, in 2015, we terminated our participation in the co-development and commercialization of brodalumab, a product candidate that was in phase 3, with AstraZeneca. The decision was based on events of suicidal ideation and behavior in the brodalumab program that occurred late in the development program, which we believed likely would necessitate restrictive labeling that would limit the appropriate patient population. Inability to bring a product to market or a significant delay in the expected approval and related launch date of a new product for any of the reasons discussed could potentially have a negative effect on our product sales and earnings and could result in a significant impairment of in-process research and development (IPR&D) or other intangible assets.

We must conduct clinical trials in humans before we commercialize and sell any of our product candidates or existing products for new indications.

Before ~~we sell any products,~~a product may be sold, we must conduct clinical trials to demonstrate that our product candidates are safe and effective for use in humans. The results of those clinical trials are used as the basis to obtain approval from regulatory authorities such as the FDA and EMA. See Our current products and products in development cannot be sold without regulatory approval. We are required to conduct clinical trials using an appropriate number of trial sites and patients to support the product label claims. The length of time, number of trial sites and number of patients required for clinical trials vary substantially, and we may spend several years and incur substantial expense in completing certain clinical trials. In addition, we may have difficulty finding a sufficient number of clinical trial sites ~~and~~and/or patients to participate in our clinical trials, particularly if competitors are conducting clinical trials in similar patient populations. See The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, supply chains, distribution systems, product development, product sales, business and results of operations. Patients may withdraw from clinical trials at any time, and privacy laws and/or other restrictions in certain countries may restrict the ability of clinical trial investigators to conduct further follow-up on such patients, which may adversely affect the interpretation of study results. Delays and complications in

planned clinical trials can result in increased development costs, associated delays in regulatory approvals and in product candidates reaching the market and revisions to existing product labels.

Further, to increase the number of patients available for enrollment in our clinical trials, we have opened, and will continue to open, clinical sites and enroll patients in a number of locations where our experience conducting clinical trials is more limited, including ~~Russia,~~ India, China, South Korea, the Philippines, Singapore and some Central and South American countries, either through utilization of third-party contract clinical trial providers entirely or in combination with local staff. Conducting clinical trials in locations where we have limited experience requires substantial time and resources to understand the unique regulatory environments of individual countries. For other examples of the risks of conducting clinical trials in China, see also Our sales and operations are subject to the risks of doing business internationally, including in emerging markets. Further, we must ensure the timely production, distribution and delivery of the clinical supply of our product candidates to numerous and varied clinical trial sites. Additionally, regional disruptions, including natural and man-made disasters, or health emergencies (such as novel viruses or pandemics such as the one we are currently experiencing with COVID-19), or geopolitical conflicts (such as the ongoing armed conflict in Ukraine) have significantly disrupted the timing of clinical trials, and in the future could ~~significantly~~ disrupt the timing, execution and outcome of clinical trials. If we fail to adequately manage the design, execution and diverse regulatory aspects of our ~~large and/or complex~~ clinical trials or to manage the production or distribution of our clinical supply, or such sites experience disruptions as a result of a natural/man-made disaster, or health emergency or geopolitical conflict, corresponding regulatory approvals may be delayed or we may fail to gain approval for our product candidates or could lose our ability to market existing products in certain therapeutic areas or altogether. For example, our clinical trials have been adversely affected by the COVID-19 pandemic. See The COVID-19 pandemic, and the public and governmental effort to mitigate against the spread of the disease, have had, and are expected to continue to have, an adverse effect, and may have a material adverse effect, on our clinical trials, operations, supply chains, distribution systems, product development, product sales, business and results of operations. If we are unable to market and sell our products or product candidates or to obtain approvals in the timeframe needed to execute our product strategies, our business and results of operations could be materially and adversely affected.

We rely on independent third-party clinical investigators to recruit patients and conduct clinical trials on our behalf in accordance with applicable study protocols, laws and regulations. Further, we rely on unaffiliated third-party vendors to perform certain aspects of our clinical trial operations. In some circumstances, we enter into co-development arrangements with other pharmaceutical and medical devices companies that provide for the other company to conduct certain clinical trials for the product we are co-developing or to develop a diagnostic test used in screening or monitoring patients in our clinical trials. See Some of our pharmaceutical pipeline and of our commercial product sales rely on collaborations with third parties, which may adversely affect the development and ~~sale~~sales of our products. We also may acquire companies that have past or ongoing clinical trials or rights to products or product candidates for which clinical trials have been or are being conducted. These trials may not have been conducted to the same standards as ours; however, once an acquisition has been completed we assume responsibility for the conduct of these trials, including any potential risks and liabilities associated with the past and prospective conduct of those trials. If regulatory authorities determine that we or others, including our licensees or co-development partners, or the independent investigators or vendors selected by us, our co-development partners or by a company we have acquired or from which we have acquired rights to a product or product candidate, have not complied with regulations applicable to the clinical trials, those authorities may refuse or reject some or all of the clinical trial data or take other actions that could delay or otherwise negatively affect our ability to obtain or maintain marketing approval of the product or indication. In addition, delays or failures to develop diagnostic tests for our clinical trials can affect the timely enrollment of such trials and lead to delays or inability to obtain marketing approval. If we were unable to market and sell our products or product candidates, our business and results of operations could be materially and adversely affected.

In addition, some of our clinical trials utilize drugs manufactured and marketed by other pharmaceutical companies. These drugs may be administered in clinical trials in combination with one of our products or product candidates or in a head-to-head study comparing the products’ or product candidates’ relative efficacy and safety. In the event that any of these vendors or pharmaceutical companies have unforeseen issues that negatively affect the quality of their work product or create a shortage of supply, or if we are otherwise unable to obtain an adequate supply of these other drugs, our ability to complete our applicable clinical trials and/or evaluate clinical results may also be negatively affected. As a result, such quality or supply problems could adversely affect our ability to timely file for, gain or maintain regulatory approvals worldwide.

Clinical trials must generally be designed based on the current standard of medical care. However, in certain diseases, such as cancer, the standard of care is evolving rapidly. In some cases, we may design a clinical trial based on the standard of care we anticipate will exist at the time our study is completed. The duration of time needed to complete certain clinical trials may result in the design of such clinical trials being based on standards of medical care that are no longer or that have not become the current standards by the time such trials are completed, limiting the utility and application of such trials. Additionally, the views of regulatory agencies relating to the requirements for accelerated approval may change over time, and trial designs that were sufficient to support accelerated approvals for some oncology products may not be considered sufficient

for later candidates. We may not obtain favorable clinical trial results and therefore may not be able to obtain regulatory approval for new product candidates or new indications for existing products and/or maintain our current product labels. Participants in clinical trials of our products and product candidates may also suffer adverse medical events or side effects that could, among other factors, delay or terminate clinical trial programs and/or require additional or longer trials to gain approval.

Even after a product is on the market, safety concerns may require additional or more extensive clinical trials as part of a risk management plan for our product or for approval of a new indication. ~~For example, in connection with the June 2011 ESA label changes, we agreed to and conducted additional clinical trials examining the use of ESAs in CKD.~~ Additional clinical trials we initiate, including those required by the FDA, could result in substantial additional expense, and the outcomes could result in further label restrictions or the loss of regulatory approval for an approved indication, each of which could have a material adverse effect on our product sales, business and results of operations. Additionally, any negative results from such trials could materially affect the extent of approvals, the use, reimbursement and sales of our products, our business and results of operations.

Our current products and products in development cannot be sold without regulatory approval.

Our business is subject to extensive regulation by numerous state and federal government authorities in the United States, including the FDA, and by foreign regulatory authorities, including the EMA. We are required in the United States and in ~~foreign~~the other regions and countries in which we, or our partners and affiliates, sell to obtain approval from regulatory authorities before we manufacture, market and sell our products. Once our products are approved, the FDA and other U.S. and ~~foreign~~ex-U.S. regulatory agencies have substantial authority to require additional testing and reporting, perform inspections, change product labeling or mandate withdrawals of our products. Failure to comply with applicable regulatory requirements may subject us to administrative and/or judicially imposed sanctions or monetary penalties as well as reputational and other harms. The sanctions could include the FDA’s or ~~foreign~~ex-U.S. regulatory authorities’ refusals to approve pending applications, delays in obtaining or withdrawals of approvals, delays or suspensions of clinical trials, warning letters, product recalls or seizures, total or partial suspensions of our operations, injunctions, fines, civil penalties and/or criminal prosecutions.

Obtaining and maintaining regulatory approvals have been, and will continue to be, increasingly difficult, time-consuming and costly. Legislative bodies or regulatory agencies could enact new laws or regulations, change existing laws or regulations or change their interpretations of laws or regulations at any time, which could affect our ability to obtain or maintain approval of our products or product candidates. The rate and degree of change in existing laws and regulations and regulatory expectations have accelerated in established markets, and regulatory expectations continue to evolve in emerging markets. We are unable to predict whether and when any further changes to laws or regulatory policies affecting our business could occur, such as changes to laws or regulations governing manufacturer communications concerning drug products and drug product candidates and whether such changes could have a material adverse effect on our product sales, business and results of operations. Further, we are reliant on regulators having the resources necessary to evaluate and approve our products. In the United States, a partial federal government shutdown halted the work of many federal agencies and their employees from late December 2018 through late January 2019. A subsequent extended shutdown could result in reductions or delays of FDA’s activities, including with respect to our ongoing clinical programs, our manufacturing of our products and product candidates and our product approvals.

Regulatory authorities have questioned, and may in the future question, the sufficiency for approval of the endpoints we select for our clinical trials. A number of our products and product candidates have been evaluated in clinical trials using surrogate endpoints that measure an effect that is known to correlate with an ultimate clinical benefit. For example, a therapeutic oncology product candidate may be evaluated for its ability to reduce or eliminate minimal residual disease (MRD), or to extend the length of time during and after the treatment that a patient lives without the disease worsening, measured by PFS. Demonstrating that the product candidate induces MRD-negative responses or produces a statistically significant improvement in PFS does not necessarily mean that the product candidate will show a statistically significant improvement in overall survival or the time that the patients remain alive. In the CV setting, a heart disease therapeutic candidate may be evaluated for its ability to reduce LDL-C levels, as an elevated LDL-C level has been a surrogate endpoint for CV events such as death, heart attack and stroke. The use of surrogate endpoints such as PFS and LDL-C reduction, in the absence of other measures of clinical benefit, may not be sufficient for broad usage or approval even when such results are statistically significant. Regulatory authorities could also add new requirements, such as the completion of enrollment in a confirmatory study or the completion of an outcomes study or a meaningful portion of an outcomes study, as conditions for obtaining approval or obtaining an indication. For example, despite demonstrating that Repatha® reduced LDL-C levels in a broad patient population, only after our large phase 3 outcomes study evaluating the ability of Repatha® to prevent CV events met certain of its primary composite endpoint and key secondary composite endpoint did the FDA grant a broader approval of Repatha® to reduce the risk of certain CV ~~events, and also to be used, alone or in combination with other lipid-lowering therapies, for the treatment of adults with primary hyperlipidemia to reduce LDL-C.~~events. There may also be situations in which demonstrating the efficacy and safety of a product candidate may not be sufficient to gain regulatory approval unless superiority to other existing treatment options can be shown. The imposition of additional requirements or our inability to meet them in a timely fashion, or at all, has delayed, and may in the future delay, our clinical development and regulatory filing efforts, delay or prevent us from obtaining regulatory approval for new product candidates or new indications for existing products, or prevent us from maintaining our current product labels.

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Some of our products have been approved by U.S. and ~~foreign~~ex-U.S. regulatory authorities on an accelerated or conditional basis with full approval conditioned upon fulfilling the requirements of regulators. For example, in ~~March 2018,~~May 2021, we announced that the FDA approved ~~BLINCYTO~~® LUMAKRAS under accelerated approval for the treatment of ~~adults and children~~adult patients with ~~B-cell precursor acute lymphoblastic leukemia (ALL) in first~~KRAS G12C-mutated local advanced or ~~second complete remission with MRD greater than or equal to 0.1 percent.~~metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. Continued approval for this indication ~~may be~~is contingent upon verification and description of clinical benefit in confirmatory ~~trials.~~trials, including a requirement by the FDA that we complete a post-marketing trial to investigate whether a lower dose will have a similar clinical effect to the results demonstrated in our pre-marketing trial. We have since received the data from such post-marketing trial and intend to submit it to the FDA, as required. Regulatory authorities are placing greater focus on monitoring products originally approved on an accelerated or conditional basis and on whether the sponsors of such products have met the conditions of the accelerated or conditional approvals. If we are unable to fulfill the regulators’ requirements that were conditions of a product’s accelerated or conditional approval and/or if regulators reevaluate the data or risk-benefit profile of our product, the conditional approval may not result in full approval or may be revoked or not renewed. Alternatively, we may be required to change the product’s labeled indications or even withdraw the product from the market.

Regulatory authorities can also impose post-marketing pediatric study requirements. Failure to fulfill such requirements may result in regulatory or enforcement action, including financial penalties or the invalidation of a product’s marketing authorization.

Safety problems or signals can arise as our products and product candidates are evaluated in clinical trials, including investigator sponsored studies, or as our marketed products are used in clinical practice. We are required continuously to collect and assess adverse events reported to us and to communicate to regulatory agencies these adverse events and safety signals regarding our products. Regulatory agencies periodically perform inspections of our pharmacovigilance processes, including our adverse event reporting. In the United States, for our products with approved REMS (see Item 1. Business—Government Regulation—Postapproval Phase), we are required to submit periodic assessment reports to the FDA to demonstrate that the goals of the REMS are being met. REMS and other risk management programs are designed to help ensure that a drug’s benefits outweigh the risks and vary in the elements they contain. If the FDA is not satisfied with the results of the periodic assessment reports we submit for any of our REMS, the FDA may also modify our REMS or take other regulatory actions, such as implementing revised or restrictive labeling. The drug delivery devices approved for use in combination with our products are also subject to regulatory oversight and review for safety and malfunctions. See Some of our products are used with drug delivery or companion diagnostic devices that have their own regulatory, manufacturing and other risks. If regulatory agencies determine that we or other parties (including our clinical trial investigators, those operating our patient support programs or licensees of our products) have not complied with the applicable reporting, other pharmacovigilance or other safety or quality assessment requirements, we may become subject to additional inspections, warning letters or other enforcement actions, including fines, marketing authorization withdrawal and other penalties. Our product candidates and marketed products can also be affected by safety problems or signals occurring with respect to products that are similar to ours or that implicate an entire class of products. Further, as a result of clinical trials, including sub-analyses or meta-analyses of earlier clinical trials (a meta-analysis involves the use of various statistical methods to combine results from previous separate but related studies) performed by us or others, concerns may arise about the sufficiency of the data or studies underlying a product’s approved label. Such actual or perceived safety problems or concerns can lead to:

•revised or restrictive labeling for our products, or the potential for restrictive labeling that has resulted, and may in the future result, in our decision not to commercialize a product candidate;

•requirement of risk management or minimization activities or other regulatory agency compliance actions related to the promotion and sale of our products;

•post-marketing commitments, mandated post-marketing requirements or pharmacovigilance programs for our approved products;

•product recalls of our approved products;

•required changes to the processes used in the manufacture of our products, which could increase our manufacturing costs and affect the availability of contract manufacturers we may utilize to assist in such manufacturing;

•revocation of approval for our products from the market completely, or within particular therapeutic areas or patient types;

•increased timelines or delays in being approved by the FDA or other regulatory bodies; and/or

•treatments or product candidates not being approved by regulatory bodies.

For example, after an imbalance in positively adjudicated CV serious adverse events was observed in one of the phase 3 clinical trials for EVENITY® but not in another, larger phase 3 study, in April 2019 the FDA approved EVENITY® for the

treatment of osteoporosis in postmenopausal women at high risk for fracture, along with a post-marketing requirement. The requirement includes a five-year observational feasibility study that could be followed by a comparative safety study or trial.

In addition to our innovative products, we are working to develop and commercialize biosimilar versions of a number of products currently manufactured, marketed and sold by other pharmaceutical companies. In some markets, there is not yet a legislative or regulatory pathway for the approval of biosimilars. In the United States, the BPCIA provided for such a ~~pathway; while~~pathway. Discussions within the FDA ~~continues to implement it, discussions~~and other regulatory authorities, and between regulatory authorities and sponsors, continue as to the evidence needed to demonstrate biosimilarity or interchangeability for specific products. See We currently face competition from biosimilars and generics and expect to face increasing competition from biosimilars and generics in the future. Delays or uncertainties in the development or implementation of such pathways, or changes in existing regulatory pathways, including degradation of regulatory standards, could result in delays or difficulties in getting our biosimilar products approved by regulatory authorities, subject us to unanticipated development costs or otherwise reduce the value of the investments we have made in the biosimilars area. Further, we cannot predict ~~whether~~the extent to which any ~~repeal or reform of the ACA or other legislation~~potential legislative or policy initiatives would affect the biosimilar pathway or have a material adverse effect on our development of biosimilars or on our marketed biosimilars. In addition, if we are unable to bring our biosimilar products to market on a timely basis and secure “first-to-market” or other advantageous positions, our future biosimilar sales, business and results of operations could be materially and adversely affected.

Some of our products are used with drug delivery or companion diagnostic devices that have their own regulatory, manufacturing and other risks.

Many of our products and product candidates may be used in combination with a drug delivery device, such as an injector or other delivery system. For example, Neulasta® is available as part of the Neulasta® Onpro® kit, and our AutoTouch® reusable autoinjector is used with ENBREL Mini® single-dose prefilled cartridges. In addition, some of our products or product candidates, including many of our oncology product candidates and products, including ~~sotorasib,~~LUMAKRAS/LUMYKRAS and bemarituzumab, may also require the use of a companion or other diagnostic device such as a device that determines whether the patient is eligible to use our drug or that helps ensure its safe and effective use. In some regions, including the United States, regulatory authorities may require contemporaneous approval of the companion diagnostic device and the therapeutic product; in others the regulatory authorities may require a separate study of the companion diagnostic device. Our product candidates or expanded indications of our products used with such devices may not be approved or may be substantially delayed in receiving regulatory approval if development or approval of such devices is delayed, such devices do not also gain or maintain regulatory approval or clearance, or if such devices do not remain commercially available. When approval of the product and device is sought under a single marketing drug application, the increased complexity of the review process may delay receipt of regulatory approval. In addition, some of these devices may be provided by single-source unaffiliated third-party companies. We are dependent on the sustained cooperation and effort of those third-party companies to supply and/or market the devices and, in some cases, to conduct the studies required for approval or clearance by the applicable regulatory agencies. We are also dependent on those third-party companies continuing to meet applicable regulatory or other requirements. Failure to successfully develop, modify, or supply the devices, delays in or failures of the Amgen or third-party studies, or failure of us or the third-party companies to obtain or maintain regulatory approval or clearance of the devices could result in increased development costs; delays in, or failure to obtain or maintain, regulatory approval; and/or associated delays in a product candidate reaching the market or in the addition of new indications for existing products. We are also required to collect and assess user complaints, adverse events and malfunctions regarding our devices, and actual or perceived safety problems or concerns with a device used with our product can lead to regulatory actions and adverse effects on our products. See Our current products and products in development cannot be sold without regulatory approval. Additionally, regulatory agencies conduct routine monitoring and inspections to identify and evaluate potential issues with our devices. For example, in 2017, the FDA reported on its adverse event reporting system that it was evaluating our Neulasta® Onpro® kit. Subsequently, we implemented device and labeling enhancements to address product complaints received on this device. We continuously monitor complaints and adverse events and implement additional enhancements as needed. Loss of regulatory approval or clearance of a device that is used with our product may also result in the removal of our product from the market. Further, failure to successfully develop, supply, or gain or maintain approval for these devices could adversely affect sales of the related approved products.

Some of our pharmaceutical pipeline and our commercial product sales rely on collaborations with third parties, which may adversely affect the development and ~~sale~~sales of our products.

We depend on alliances with other companies, including pharmaceutical and biotechnology companies, vendors and service providers, for the development of a portion of the products in our pharmaceutical pipeline and for the commercialization and sales of certain of our commercial products. For example, we have collaborations with third parties under which we share development rights, obligations and costs and/or commercial rights and obligations. See Item 1. Business—Business Relationships.

Failures by these parties to meet their contractual, regulatory, or other obligations to us or any disruption in the relationships between us and these third parties, could have a material adverse effect on our pharmaceutical pipeline and business. In addition, our collaborative relationships for R&D and/or commercialization and sales often extend for many years and have given, and may in the future give, rise to disputes regarding the relative rights, obligations and revenues of us and our collaboration partners, including the ownership or prosecution of intellectual property and associated rights and obligations. This could result in the loss of intellectual property rights or protection, delay the development and sale of potential pharmaceutical products, affect the ~~effective~~ sale and delivery of our commercialized products and lead to lengthy and expensive litigation, administrative proceedings or arbitration. ~~For example, we are currently involved in litigation with Novartis over our collaboration agreements for the development and commercialization of Aimovig~~®. See Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements. While our collaboration remains in place until the litigation is resolved and we remain committed to continuing to work with Novartis to sell and deliver Aimovig®, it is possible that the dispute may nevertheless affect the efficiency of operation and future growth of the collaboration. The litigation may also affect or delay, or lead to a termination of, other projects with Novartis.

Our efforts to collaborate with or acquire other companies, products, or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful, and may result in unanticipated costs, delays or failures to realize the benefits of the transactions.

We seek innovation through significant investment in both internal R&D and external transactions, including collaborations, ~~partnering,~~partnerships, alliances, licenses, joint ventures, mergers and acquisitions (collectively, acquisition activity). Acquisition activities may be subject to regulatory approvals or other requirements that are not within our control. There can be no assurance that such regulatory or other approvals will be obtained or that all closing conditions required in connection with our acquisition activities will be satisfied or waived, which could result in us being unable to complete the planned acquisition activities. In addition, antitrust scrutiny by regulatory agencies and changes to regulatory approval process in the U.S. and foreign jurisdictions may cause approvals to take longer than anticipated to obtain, not be obtained at all, or contain burdensome conditions, which may jeopardize, delay or reduce the anticipated benefits of acquisitions to us and could impede the execution of our business strategy.

Acquisition activities are complex, time consuming and expensive and may result in unanticipated costs, delays or other operational or financial problems related to integrating the acquired company and business with our company, which may divert our management’s attention from other business issues and opportunities and restrict the full realization of the anticipated benefits of such transactions within the expected timeframe or at all. We may pay substantial amounts of cash, incur debt or issue equity securities to pay for acquisition activities, which could adversely affect our liquidity or result in dilution to our stockholders, respectively. Further, failures or difficulties in integrating or retaining new personnel or in integrating the operations of the businesses, products or assets we acquire (including related technology, commercial operations, compliance programs, manufacturing, distribution and general business operations and ~~procedures)~~procedures and ESG activities) may affect our ability to realize the benefits of the transaction and grow our business and may result in us incurring asset impairment or restructuring charges. These and other challenges may arise in connection with our ~~recent acquisition~~acquisitions of Otezla,® Five Prime, Teneobio, ChemoCentryx, Horizon and/or ~~collaboration~~our collaborations with BeiGene and KKC, or with other acquisition activities, which could have a material adverse effect on our business, results of operations and stock price.

RISKS RELATED TO OPERATIONS

We perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California; significant disruptions or production failures at these facilities could significantly impair our ability to supply our products or continue our clinical trials.

The global supply of our products and product candidates for commercial sales and for use in our clinical trials is significantly dependent on the uninterrupted and efficient operation of our manufacturing facilities, in particular those in the U.S. territory of Puerto Rico and Thousand Oaks, California. See Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

We currently perform a substantial majority of our clinical manufacturing that supports our product candidates at our facility in Thousand Oaks, California. A substantial disruption in our ability to operate our Thousand Oaks manufacturing facility could materially and adversely affect our ability to supply our product candidates for use in our clinical trials, leading to delays in development of our product candidates.

In addition, we currently perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico. In recent years, Puerto Rico has been affected by a number of natural disasters, including ~~droughts in mid-2020,~~Hurricane Maria (2017), earthquakes ~~in early 2020~~(2020) and Hurricane ~~Maria in 2017.~~Fiona (2022). These natural disasters have affected, and may continue to affect, public and private properties and Puerto Rico’s electric grid and communications ~~networks in the future.~~networks. While the critical manufacturing areas of our commercial manufacturing facility were not significantly affected by these natural disasters, the restoration of electrical service on the island after Hurricane Maria was a slow process, and our facility ~~operated with electrical power from~~relied on backup diesel powered generators for some time. We also operated on backup generators for a few weeks after the early 2020 earthquakes in Puerto Rico. In 2021, the baseload power generation units of the Puerto Rico Electric Power Authority malfunctioned due to the

lack of adequate maintenance for over a decade, leading to selective outages across the island. In September 2022, Hurricane Fiona caused further damage to the island’s utility infrastructure which again resulted in widespread power outages and water supply issues. Although these events did not directly have a material effect on our business, they have resulted in disruptions to our third-party suppliers on the island. Further instability of the electric grid could require us to increase ~~the~~our use of our generators or to ~~continue using~~use them exclusively. In addition, future storms, earthquakes or other natural or man-made disasters or events (including political unrest or labor shortages) could ~~cause~~have a more significant effect on our manufacturing operations. ~~Puerto Rico and the rest of the world are facing the effects of the~~The COVID-19 pandemic ~~and~~has also resulted in disruptions to activities on the ~~associated health and economic implications. Since March2020,~~island. In March 2020, the Governor of Puerto Rico issued Executive Orders requiring the lockdown of businesses and government facilities, imposing restrictions on business operations and a curfew on ~~residents. Our operations~~residents in response to COVID-19. Additionally, during the summer of 2021, a labor dispute arose between the maritime terminal operation company and its employees, ~~have been exempted~~represented by the International Longshoremen’s Association (ILA), which resulted in a strike that delayed cargo movement from the ~~lockdown~~San Juan Port Zone for several days. Hurricanes Maria and ~~curfew, but we cannot predict how long these orders will continue in effect and what impact these orders and~~Fiona, the 2020 earthquakes, the COVID-19 pandemic ~~will~~and the ILA strike have also placed greater stress on ~~our future operations,~~the island’s already challenged economy. Beginning in 2016, the government of Puerto Rico defaulted on its roughly $72 billion of debt. In response, the U.S. Congress passed the Puerto Rico Oversight, Management, and ~~whether the Governor will issue future Executive Orders imposing stricter lockdown and curfew measures should COVID-19 cases rise in~~Economic Stability Act, which established a financial oversight board for Puerto Rico. After years of negotiations with bondholders and other creditors, this financial oversight board reached an agreement with the same, which was confirmed by the U.S. District Court for the District of Puerto Rico effective March 2022. Although our ability to manufacture and supply our products has not, to date, been significantly affected by ~~these~~ natural disasters, unreliable electric utility services, strikes, pandemic lockdowns or the ~~COVID-19 pandemic,~~island’s economic challenges, these, or a combination of these challenges, or other issues that ~~could give rise to any~~create a substantial disruption to our ability to operate our Puerto Rico manufacturing facility or get supplies and manufactured products transported to and from that location, could make it more expensive or difficult for us to operate in Puerto Rico, and could materially and adversely affect our ability to supply our products and affect our product sales. See Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product ~~sales.~~sales

Hurricane Maria, the earthquakes of early 2020 and the COVID-19 pandemic have placed greater stress on the island’s already challenged economy. Beginning in 2016, the government of Puerto Rico defaulted on its roughly $72 billion in debt. In response, the U.S. Congress passed the Puerto Rico Oversight, Management, and Economic Stability Act (PROMESA), which established a Financial Oversight and Management Board (Oversight Board) to provide fiscal oversight. Title III of PROMESA provides Puerto Rico with a judicial process for restructuring its debt similar to, but not identical to, Chapter 9 of the U.S. Bankruptcy Code, including a stay of debtholder litigation. In 2017, the Oversight Board approved and certified the filing in the U.S. District Court for the District of Puerto Rico of a voluntary petition under Title III of PROMESA for the government of Puerto Rico and certain of its governmental entities, including the Puerto Rico Electric Power Authority, which is currently undergoing a privatization process of its transmission and distribution infrastructure. Under PROMESA, other Title III filings for additional government entities may occur, further complicating Puerto Rico’s already uncertain fiscal stability. In June 2019, in response to legal challenges, the U.S. Supreme Court ruled in favor of PROMESA and confirmed the constitutionality of the appointment process.

Each year since 2017, the Oversight Board has updated Puerto Rico’s fiscal plans imposing significant expense reductions. Each plan has stressed the need for fiscal and structural reforms to address Puerto Rico’s challenging economic and demographic trends. There is pending litigation between the Government of Puerto Rico and the Oversight Board with regards to the Oversight Board’s powers under PROMESA and authority to review and prevent the enforcement of government-approved legislation. This litigation, currently underway in the Title III Court, may impact how and when Puerto Rico will eventually restructure its debt and achieve fiscal and economic stability.

While the government and the Oversight Board have authorized emergency relief packages due to the COVID-19 pandemic, it is uncertain how, or the degree to which, the pandemic will impact Puerto Rico’s fiscal and structural reforms and its economy. In addition, the 2017 Tax Act no longer permits deferral of U.S. taxation on Puerto Rico earnings, although these earnings generally will be taxed in the United States at a reduced rate. Given Puerto Rico’s challenged economy, disaster recovery needs and impact from the COVID-19 pandemic, it may be difficult for Puerto Rico to sustain or grow its manufacturing base, which contributes significantly to Puerto Rico’s economy, due to competition from other locations subject to similar levels of taxation.

While PROMESA and the actions above continue to be important factors in moving Puerto Rico toward economic stability, Puerto Rico’s ongoing economic and demographic trend challenges and political situation, the effects of natural disasters, the COVID-19 pandemic, and the effects of the 2017 Tax Act or other potential tax law changes have negatively affected, and may in the future negatively affect, the territorial government’s provision of utilities or other services in Puerto Rico that we use in the operation of our business and could create the potential for increased taxes or fees to operate in Puerto Rico, result in a migration of workers from Puerto Rico to the mainland United States, or make it more expensive or difficult for us to operate in Puerto Rico. These factors could have a material adverse effect on our ability to supply our products, on our business and on our product sales.

We rely on third-party suppliers for certain of our raw materials, medical devices and components.

We rely on unaffiliated third-party suppliers for certain raw materials, medical devices and components necessary for the manufacturing of our commercial and clinical products. Certain of those raw materials, medical devices and components are proprietary products of those unaffiliated third-party suppliers and are specifically cited in our drug applications with regulatory agencies so that they must be obtained from that specific sole source or sources and could not be obtained from another supplier unless and until the regulatory agency approved such supplier. For example, ~~Scandinavian Health Limited Group is our~~we rely on a single source offor the SureClick® autoinjectors ~~for~~used in the drug delivery of Repatha,®, ENBREL, Aimovig,®, AMGEVITATM and ~~Aranesp~~®.Aranesp. Also, certain of the raw materials required in the commercial and clinical manufacturing of our products are sourced from other countries and/or derived from biological sources, including mammalian tissues, bovine serum and human serum albumin.

Among the reasons we may be unable to obtain these raw materials, medical devices and components include:

•regulatory requirements or action by regulatory agencies or others;

•adverse financial or other strategic developments at or affecting the supplier, including bankruptcy;

•unexpected demand for or shortage of raw materials, medical devices or components;

•failure to comply with our quality standards which results in quality and product failures, product contamination and/or recall;

•a material shortage, contamination, recall and/or restrictions on the use of certain biologically derived substances or other raw materials;

•discovery of previously unknown or undetected imperfections in raw materials, medical devices or components;

•cyberattacks on supplier systems; ~~and~~

•natural or other disasters, including hurricanes, earthquakes, volcanoes or fires;

•labor disputes or shortages, including from the effects of health emergencies (such as novel viruses or pandemics such as the one we are currently experiencing with COVID-19) ~~and~~or natural ~~disasters.~~disasters; and

•geopolitical conflicts.

For example, in prior years we have experienced shortages in certain components necessary for the formulation, fill and finish of certain of our products in our Puerto Rico ~~facility.~~facility, and we have also experienced shortages related to single use systems and packaging which has caused disruptions to our manufacturing plans. Further quality issues that result in

unexpected additional demand for certain components have resulted in shortages and in the future may lead to shortages of required raw materials or components (such as we have experienced with EPOGEN® glass vials). We may experience similar or other shortages in the future resulting in delayed shipments, supply constraints, clinical trial delays, contract disputes and/or stock-outs of our products. These or other similar events could negatively affect our ability to satisfy demand for our products or conduct clinical trials, which could have a material adverse effect on our product sales, business and results of operations.

Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

Manufacturing biologic and small molecule human therapeutic products is difficult, complex and highly regulated. We manufacture many of our commercial products and product candidates internally. In addition, we currently use third-party contract manufacturers to produce, or assist in the production of, a number of our products, and we currently use contract manufacturers to produce, or assist in the production of, a number of our late-stage product candidates and drug delivery devices. See Item 1. Business—Manufacturing, Distribution and Raw Materials—Manufacturing. Our ability to adequately and timely manufacture and supply our products (and product candidates to support our clinical trials) is dependent on the uninterrupted and efficient operation of our facilities and those of our third-party contract manufacturers, which may be affected by:

•capacity of manufacturing facilities;

•contamination by microorganisms or viruses, or foreign particles from the manufacturing process;

•natural or other disasters, including hurricanes, earthquakes, volcanoes or fires;

•labor disputes or shortages, including the effects of health emergencies (such as novel viruses or pandemics such as the one we are currently experiencing with COVID-19) or natural disasters;

•compliance with regulatory requirements;

•changes in forecasts of future demand;

•timing and actual number of production runs and production success rates and yields;

•updates of manufacturing specifications;

•contractual disputes with our suppliers and contract manufacturers;

•timing and outcome of product quality testing;

•power failures and/or other utility failures;

•cyberattacks on supplier systems;

•breakdown, failure, substandard performance or improper installation or operation of equipment (including our information technology systems and network-connected control systems or those of our contract manufacturers or third-party service providers); ~~and/or~~

•delays in the ability of the FDA or foreign regulatory agencies to provide us necessary reviews, inspections and approvals, including as a result of a subsequent extended U.S. federal or other government ~~shutdowns.~~shutdowns; and/or

•geopolitical conflicts.

If any of these or other problems affect production in one or more of our facilities or those of our third-party contract manufacturers, or if we do not accurately forecast demand for our products or the amount of our product candidates required in clinical trials, we may be unable to start or increase production in our unaffected facilities to meet demand. If the efficient manufacture and supply of our products or product candidates is interrupted, we may experience delayed shipments, delays in our clinical trials, supply constraints, stock-outs, adverse event trends, contract disputes and/or recalls of our products. From time to time, we have initiated recalls of certain lots of our products. For example, in July 2014 we initiated a voluntary recall of an Aranesp® lot distributed in the EU after particles were detected in a quality control sample following distribution of that lot, and in April 2018 we initiated a precautionary recall of two batches of Vectibix® distributed in Switzerland after potential crimping defects were discovered in the metal seals on some product vials. If we are at any time unable to provide an uninterrupted supply of our products to patients, we may lose patients and physicians may elect to prescribe competing therapeutics instead of our products, which could have a material adverse effect on our product sales, business and results of operations.

Our manufacturing processes, those of our third-party contract manufacturers and those of certain of our third-party service providers must undergo regulatory approval processes and are subject to continued review by the FDA and other regulatory authorities. It can take longer than five years to build, validate and license another manufacturing plant, and it can take longer than three years to qualify and license a new contract manufacturer or service provider. If we elect or are required to make changes to our manufacturing processes because of new regulatory requirements, new interpretations of existing requirements or other reasons, this could increase our manufacturing costs and result in delayed shipments, delays in our clinical trials, supply constraints, stock-outs, adverse event trends or contract negotiations or disputes. Such manufacturing challenges may also occur if our existing contract manufacturers are unable or unwilling to timely implement such changes, or at all.

In addition, regulatory agencies conduct routine monitoring and ~~conduct~~ inspections of our manufacturing facilities and processes as well as those of our third-party contract manufacturers and service providers. If regulatory authorities determine that we or our third-party contract manufacturers or certain of our third-party service providers have violated regulations, they may mandate corrective actions and/or issue warning letters, or even restrict, suspend or revoke our prior approvals, prohibiting us from manufacturing our products or conducting clinical trials or selling our marketed products until we or the affected third-party contract manufacturers or third-party service providers comply, or indefinitely. See also Our current products and products in development cannot be sold without regulatory approval. Such issues may also delay the approval of product candidates we have submitted for regulatory review, even if such product candidates are not directly related to the products, devices or processes at issue with regulators. Because our third-party contract manufacturers and certain of our third-party service providers are subject to the FDA and foreign regulatory authorities, alternative qualified third-party contract manufacturers and third-party service providers may not be available on a timely basis, or at all. If we or our third-party contract manufacturers or third-party service providers cease or interrupt production or if our third-party contract manufacturers and third-party service providers fail to supply materials, products or services to us, we may experience delayed shipments, delays in our clinical trials, supply constraints, contract disputes, stock-outs and/or recalls of our products. Additionally, we distribute a substantial volume of our commercial products through our primary distribution centers in Louisville, Kentucky for the United States and in Breda, Netherlands for Europe and much of the rest of the world. We also conduct most of the labeling and packaging of our products distributed in Europe and much of the rest of the world in Breda. Our ability to timely supply products is dependent on the uninterrupted and efficient operations of our distribution and logistics centers, our third-party logistics providers and our labeling and packaging facility in Breda. Further, we rely on commercial transportation, including air and sea freight, for the distribution of our products to our customers, which has been negatively affected by the ongoing COVID-19 pandemic and may be negatively affected by natural disasters or geopolitical security ~~threats and/or the ongoing COVID-19 pandemic.~~threats.

There have also been legislative and administrative proposals seeking to incentivize greater drug manufacturing in the United States with the stated goal of improving supply reliability in the United States. For example, on August 6, 2020, the previous Administration issued an Executive Order aimed at boosting domestic production of essential medicines, medical countermeasures, and critical inputs titled “Executive Order on Ensuring Essential Medicines, Medical Countermeasures, and Critical Inputs are Made in the United States.” Additionally, one legislative proposal would ~~prohibit~~have prohibited the U.S. Department of Veterans Affairs from purchasing certain drugs that have active pharmaceutical ingredients manufactured outside the United States. While we perform a substantial majority of our commercial manufacturing activities in the United States, including in the U.S. territory of Puerto Rico, and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California, the passage of such legislation could result in foreign governments enacting retaliatory legislation or regulatory actions, which may have an adverse effect on our product sales, business and results of operations.

Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives.

We continue to work towards operating our business in an environmentally responsible and socially inclusive manner. Stakeholders, including our investors and our employees, have increasingly focused on, and are expected to continue to focus on, our ESG practices. If our ESG practices fail to meet these stakeholders’ expectations and standards, there could be a material adverse effect on our reputation, business and, ultimately, our stock price.

Our ESG report is made available on our website and describes our ESG goals and the progress we have made on the ESG issues deemed most important to our external and internal stakeholders, based on surveys, interviews and certain frameworks for corporate responsibility. Achieving our ESG goals requires long-term investments and broad, coordinated activity, and we may be required to incur additional costs or allocate additional resources towards monitoring, reporting and implementing our ESG practices. Further, we may fail to accurately assess our stakeholders’ ESG priorities, as such priorities have evolved and will continue to evolve. While we have achieved most of our goals set in prior years, whether we can achieve our current and future ESG goals continues to be uncertain and remains subject to numerous risks, including evolving regulatory requirements and social expectations affecting ESG practices, our ability to recruit, develop and retain a diverse workforce, the availability of suppliers and collaboration partners that can meet our ESG goals, the effects of the organic growth of our business and potential

acquisitions of other businesses on our ESG performance, and the availability and cost of technologies or resources, such as carbon credits, that support our goals. For example, impacts on the commodity market and supply chains caused by the armed conflict in Ukraine could limit the availability of electric vehicle components, impairing our ability to meet some of our environmental sustainability goals. Any failure or perceived failure to meet our ESG program priorities could result in a material adverse effect on our reputation, business and stock price.

The effects of global climate change and related natural disasters could negatively affect our business and operations.

Many of our operations and facilities, including those essential to our manufacturing, R&D and distribution activities, are in locations that are subject to natural disasters, including droughts, fires, extreme temperatures, hurricanes, tropical storms and/or floods. For example, in 2017 Hurricane Maria caused catastrophic damage, compounded in 2022 by Hurricane Fiona, to the U.S. territory of Puerto Rico, where we perform a substantial majority of our commercial manufacturing activities. Although our site was well-protected and suffered minimal damage, there can be no assurances that we would have similar results in the face of future natural disasters. The severity and frequency of weather-related natural disasters has been amplified, and is expected to continue to be amplified by, global climate change. Such natural disasters have caused, and in the future may cause, damage to and/or disrupt our operations, which may result in a material adverse effect on our product sales, business and results of operations. Our suppliers, vendors and business partners also face similar risks, and any disruption to their operations could have an adverse effect on our supply and manufacturing chain. Further, many of our key facilities are located on islands, including Puerto Rico, Singapore and Ireland, which rely on essential port facilities that may be vulnerable to climate change-related or other natural disasters. Although we have detailed business continuity plans in place and periodic assessments of our natural disaster risk, any natural disaster may also result in prolonged interruption to our critical operational and business activities, and we may be required to incur significant costs to remedy the effects of such natural disasters and fully resume operations, which may result in a material adverse effect on our product sales, business and results of operations. See We perform a substantial majority of our commercial manufacturing activities at our facility in the U.S. territory of Puerto Rico and a substantial majority of our clinical manufacturing activities at our facility in Thousand Oaks, California; significant disruptions or production failures at these facilities could significantly impair our ability to supply our products or continue our clinical trials and Manufacturing difficulties, disruptions or delays could limit supply of our products and limit our product sales.

GENERAL RISK FACTORS

Global economic conditions may negatively affect us and may magnify certain risks that affect our business.

Our operations and performance have been, and may continue to be, affected by global economic conditions. The economic downturn resulting from the COVID-19 pandemic ~~has~~ precipitated a global recession, and together with high rates of inflation and energy supply issues experienced in certain regions, have led to regional and/or global macroeconomic challenges, the effects of which may be of an extended duration. In particular, acute rising energy costs may further adversely affect productivity and economic conditions in Europe. Additionally, financial pressures may cause government or other third-party payers to more aggressively seek cost containment ~~measures.~~measures in healthcare and other settings. See Our sales depend on coverage and reimbursement from government and commercial third-party payers, and pricing and reimbursement pressures ~~may~~have affected, and are likely to continue to affect, our ~~profitability~~profitability. . As a result of global economic conditions, some third-party payers may delay or be unable to satisfy their reimbursement obligations. Job losses or other economic hardships (including inflation) may also affect patients’ ability to afford ~~health care~~healthcare as a result of increased co-pay or deductible obligations, greater cost sensitivity to existing co-pay or deductible obligations, lost healthcare insurance coverage or for other reasons. We believe such conditions have led and could continue to lead to reduced demand for our products, which could have a material adverse effect on our product sales, business and results of operations. The current inflationary environment related to increased aggregate demand, supply chain constraints and the effects from the armed conflict in Ukraine (including the effects of the sanctions that were implemented in response to the conflict and the resulting impacts on the commodity market and supply chains) have also increased our operating expenses and may continue to affect our operating expenses. Our operational costs, including the cost of energy, materials, labor, distribution and our other operational and facilities costs are subject to market conditions and are being adversely affected by inflationary pressures. Economic conditions may also adversely affect the ability of our distributors, customers and suppliers to obtain the liquidity required to buy inventory or raw materials and to perform their obligations under agreements with us, which could disrupt our operations. Although we monitor our distributors’, customers’ and suppliers’ financial condition and their liquidity to mitigate our business risks, some of our distributors, customers and suppliers may become insolvent, which could have a material adverse effect on our product sales, business and results of operations. A significant worsening of global economic conditions could precipitate or materially ~~increase these~~amplify the other risks ~~facing us.~~described herein.

We maintain a significant portfolio of investments disclosed as cash equivalents and marketable securities on our ~~Consolidated Balance Sheets.~~consolidated balance sheets. The global spread of COVID-19 has also led to disruption and volatility in the global capital markets. We have certain assets, including equity investments, that are exposed to market fluctuations that could, in a sustained

or recurrent series of market disruptions, result in impairments. The value of our investments may also be adversely affected by interest rate fluctuations, inflation, downgrades in credit ratings, illiquidity in the capital markets and other factors that may result in other-than-temporary declines in the value of our investments. Any of those events could cause us to record impairment charges with respect to our investment portfolio or to realize losses on sales of investments.

Our stock price is volatile.

Our stock price, like that of our peers in the biotechnology and pharmaceutical industries, is volatile. Our revenues and operating results may fluctuate from period to period for a number of reasons. Events such as a delay in product development, changes to our expectations or strategy or even a relatively small revenue shortfall may cause financial results for a period to be below our expectations or projections. As a result, our revenues and operating results and, in turn, our stock price may be subject to significant fluctuations. Announcements or discussions, including via social media channels, of possible restrictive actions by government or private payers that would negatively affect our business or industry if ultimately enacted or adopted may also cause our stock price to fluctuate, whether or not such restrictive actions ever actually occur. Similarly, actual or perceived safety issues with our products or similar products or unexpected clinical trial results can have an immediate and rapid effect on our stock price, whether or not our operating results are materially affected.

We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

The capital and credit markets may experience extreme volatility and disruption, which may lead to uncertainty and liquidity issues for both borrowers and investors. For example, early in 2020, there were significant disruptions in the commercial paper market and several borrowers were unable to obtain funding at normal rates or maturities, which resulted in a significant increase in draws of corporate credit lines with banks. Similarly, the bond markets experienced extreme volatility in terms of interest rates and credit spreads, with several days without new issuances of corporate bonds. We expect to access the capital markets, from time to time, to supplement our existing funds and cash generated from operations ~~in satisfying~~to satisfy our needs for working capital; capital expenditure and debt service requirements; our plans to pay dividends and repurchase stock; and other business initiatives we strategically plan to pursue, including acquisitions (such as our acquisition of Horizon) and licensing activities. In the event of adverse capital and credit market conditions, we may be unable to obtain capital market financing on similar favorable terms, or at all, which could have a material adverse effect on our business and results of ~~operations.~~operations or our ability to complete business acquisitions. Changes in credit ratings issued by nationally recognized credit-rating agencies could adversely affect our ability to obtain capital market financing and the cost of such financing and have an adverse effect on the market price of our securities.


Item 1B.			UNRESOLVED STAFF COMMENTS

None.

5451


Item 2.			PROPERTIES

As of December 31, ~~2020,~~2022, we owned or leased approximately ~~180~~150 properties. The locations and primary functions of significant properties are summarized in the following tables:

U.S. Location:

Manufacturing

Administrative

R&D

Sales & marketing

Warehouse

Distribution center

Thousand Oaks, CA*

San Francisco, CA

Louisville, KY

Cambridge, MA

~~Woburn, MA~~

Juncos, Puerto Rico

West Greenwich, RI

Tampa, FL

Other U.S. cities

* Corporate headquarters

~~Ex-U.S.~~ROW Location:

Manufacturing

Administrative

R&D

Sales & marketing

Warehouse

Distribution center

Brazil

Canada

China

Denmark

Germany

Iceland

Ireland

Japan

Netherlands

Singapore

Switzerland

~~Turkey~~

United Kingdom

Other countries

Excluded from the information above are (i) undeveloped land and leased properties that have been abandoned and (ii) certain buildings we still own but that are no longer used in our business. There are no material encumbrances on our owned properties.

We believe our facilities are suitable for their intended uses and, in conjunction with our third-party contract manufacturing agreements, provide adequate capacity and are sufficient to meet our expected needs. See Item 1A. Risk Factors for a discussion of the factors that could adversely impact our manufacturing operations and the global supply of our products.

See Item 1. Business—Manufacturing, Distribution and Raw Materials.


Item 3.			LEGAL PROCEEDINGS

Certain of the legal proceedings in which we are involved are discussed in Part IV—Note 19, Contingencies and commitments, to the Consolidated Financial Statements and are hereby incorporated by reference.


Item 4.			MINE SAFETY DISCLOSURES

Not applicable.

5552

PART II


Item 5.			MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES

Common stock

Our common stock trades on the NASDAQ Global Select Market under the symbol AMGN. As of February ~~3, 2021,~~6, 2023, there were approximately ~~5,336~~4,838 holders of record of our common stock.

Performance graph

The following graph shows the value of an investment of $100 on December 31, ~~2015,~~2017, in each of Amgen common stock, the Amex Biotech Index, the Amex Pharmaceutical Index and Standard & Poor’s 500 ~~Index (S&P 500).~~Index. All values assume reinvestment of the pretax value of dividends and are calculated as of December 31 of each year. The historical stock price performance of the Company’s common stock shown in the performance graph is not necessarily indicative of future stock price performance.


		12/31/2015	12/31/2016	12/31/2017	12/31/2018	12/31/2019	12/31/2020		12/31/2017	12/31/2018	12/31/2019	12/31/2020	12/31/2021	12/31/2022
Amgen (AMGN)	Amgen (AMGN)	$100.00	$92.45	$113.08	$130.14	$166.09	$162.76	Amgen (AMGN)	$100.00	$115.08	$146.87	$143.93	$145.19	$174.94
Amex Biotech (BTK)	Amex Biotech (BTK)	$100.00	$80.85	$111.42	$111.72	$134.54	$152.81	Amex Biotech (BTK)	$100.00	$100.26	$120.75	$137.14	$132.31	$127.01
Amex Pharmaceutical (DRG)	Amex Pharmaceutical (DRG)	$100.00	$91.66	$106.90	$114.86	$135.96	$147.86	Amex Pharmaceutical (DRG)	$100.00	$107.45	$127.20	$138.31	$170.64	$183.88
S&P 500 (SPX)		$100.00	$111.95	$136.46	$130.50	$171.57	$203.12
Standard & Poor’s 500 (SPX)								Standard & Poor’s 500 (SPX)	$100.00	$95.63	$125.73	$148.86	$191.54	$156.74


Delaware						95-3540776
(State or other jurisdiction of incorporation or organization)						(I.R.S. Employer Identification No.)
One Amgen Center Drive						91320-1799
Thousand Oaks
California
(Address of principal executive offices)						(Zip Code)


Title of each class	Trading Symbol (s)	Name of each exchange on which registered
Common stock, $0.0001 par value	AMGN	The Nasdaq Stock Market LLC
~~1.250% Senior Notes Due 2022~~	~~AMGN22~~	~~The Nasdaq Stock Market LLC~~
2.00% Senior Notes ~~Due~~due 2026	AMGN26	The Nasdaq Stock Market LLC


		Page No.
	DEFINED TERMS AND PRODUCTS	ii
PART I		1
Item 1.	BUSINESS	1
	Significant Developments	1
	Marketing, Distribution and Selected Marketed Products	3
	Reimbursement	109
	Manufacturing, Distribution and Raw Materials	1211
	Government Regulation	13
	Research and Development and Selected Product Candidates	1716
	Business Relationships	2322
	Human Capital Resources	2423
	Information about our Executive Officers	26
	Geographic Area Financial Information	27
	Investor Information	27
Item 1A.	RISK FACTORS	27
Item 1B.	UNRESOLVED STAFF COMMENTS	5451
Item 2.	PROPERTIES	5552
Item 3.	LEGAL PROCEEDINGS	5552
Item 4.	MINE SAFETY DISCLOSURES	5552
PART II		5653
Item 5.	MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES	5653
Item 6.	~~SELECTED FINANCIAL DATA~~RESERVED	5854
Item 7.	MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS	5955
Item 7A.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	7875
Item 8.	FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA	8077
Item 9.	CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE	8077
Item 9A.	CONTROLS AND PROCEDURES	8178
Item 9B.	OTHER INFORMATION	8380
PART III		8380
Item 10.	DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE	8380
Item 11.	EXECUTIVE COMPENSATION	8380
Item 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS	8481
Item 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS AND DIRECTOR INDEPENDENCE	8582
Item 14.	PRINCIPAL ~~ACCOUNTING~~ACCOUNTANT FEES AND SERVICES	8582
PART IV		8683
Item 15.	EXHIBITS AND FINANCIAL STATEMENT SCHEDULES	8683
Item 16.	FORM 10-K SUMMARY	9289
SIGNATURES		9390


		Total number of shares purchased	Average price paid per share(1)		Total number of shares purchased as part of publicly announced program	Maximum dollar value that may yet be purchased under the program(2)			Total number of shares purchased	Average price paid per share(1)		Total number of shares purchased as part of publicly announced program	Maximum dollar value that may yet be purchased under the program(2)
October 1 - October 31	October 1 - October 31	1,774,922	$	235.06	1,774,922	$	3,781,230,811	October 1 - October 31	—			—	$	6,979,263,848
November 1 - November 30	November 1 - November 30	1,660,605	$	229.16	1,660,605	$	3,400,688,112	November 1 - November 30	—			—	$	6,979,263,848
December 1 - December 31	December 1 - December 31	1,868,786	$	226.94	1,868,786	$	2,976,579,948	December 1 - December 31	—			—	$	6,979,263,848
		5,304,313	$	230.35	5,304,313				—			—
January 1 - December 31(3)	January 1 - December 31(3)	15,190,194	$	230.24	15,190,194			January 1 - December 31(3)	26,147,900	$	241.32	26,147,900


	Years ended December 31,
Consolidated Statements of Income Data:	2020		2019		2018		2017		2016
	(In millions, except per-share data)
Revenues:
Product sales	$	24,240	$	22,204	$	22,533	$	21,795	$	21,892
Other revenues	1,184		1,158		1,214		1,054		1,099
Total revenues	$	25,424	$	23,362	$	23,747	$	22,849	$	22,991
Operating expenses:
Cost of sales	$	6,159	$	4,356	$	4,101	$	4,069	$	4,162
Research and development	$	4,207	$	4,116	$	3,737	$	3,562	$	3,840
Selling, general and administrative	$	5,730	$	5,150	$	5,332	$	4,870	$	5,062
Net income(1)	$	7,264	$	7,842	$	8,394	$	1,979	$	7,722
Diluted earnings per share(1)	$	12.31	$	12.88	$	12.62	$	2.69	$	10.24
Dividends paid per share	$	6.40	$	5.80	$	5.28	$	4.60	$	4.00

	As of December 31,
Consolidated Balance Sheets Data:	2020		2019		2018		2017		2016
	(In millions)
Total assets	$	62,948	$	59,707	$	66,416	$	79,954	$	77,626
Total debt(2)	$	32,986	$	29,903	$	33,929	$	35,342	$	34,596
Total stockholders’ equity(3)	$	9,409	$	9,673	$	12,500	$	25,241	$	29,875


☒			ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934


☐			TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934


Term			Description
Acapatamab			Acapatamab (formerly AMG 160)
Aimovig			Aimovig® (erenumab-aooe)
AMGEVITA			AMGEVITA™ (adalimumab)
AMJEVITA			AMJEVITA™ (adalimumab-atto)
Aranesp			Aranesp® (darbepoetin alfa)
AutoTouch			AutoTouch®
AVSOLA			AVSOLA® (infliximab-axxq)
BLINCYTO			BLINCYTO® (blinatumomab)

Corlanor			Corlanor® (ivabradine)
Efavaleukin alfa			Efavaleukin alfa (formerly AMG 592)
Emirodatamab			Emirodatamab (formerly AMG 427)
ENBREL			Enbrel® (etanercept)
ENBREL Mini			ENBREL Mini®
EPOGEN			EPOGEN® (epoetin alfa)
EVENITY			EVENITY® (romosozumab-aqqg)
IMLYGIC			IMLYGIC® (talimogene laherparepvec)
KANJINTI			KANJINTI® (trastuzumab-anns)
KYPROLIS			KYPROLIS® (carfilzomib)
LUMAKRAS/LUMYKRAS			LUMAKRAS® / LUMYKRAS™ (sotorasib)
MVASI			MVASI® (bevacizumab-awwb)
Neulasta			Neulasta® (pegfilgrastim)
NEUPOGEN			NEUPOGEN® (filgrastim)
Nplate			Nplate® (romiplostim)
Olpasiran			Olpasiran (formerly AMG 890)
Onpro			Onpro®
Ordesekimab			Ordesekimab (formerly AMG 714)
Otezla			Otezla® (apremilast)
Parsabiv			Parsabiv® (etelcalcetide)
Prolia			Prolia® (denosumab)
Repatha			Repatha® (evolocumab)
RIABNI			RIABNI® (rituximab-arrx)
Rocatinlimab			Rocatinlimab (formerly AMG 451)
Rozibafusp alfa			Rozibafusp alfa (formerly AMG 570)
Sensipar/Mimpara			Sensipar®/Mimpara™ (cinacalcet)
SureClick			SureClick®
Tarlatamab			Tarlatamab (formerly AMG 757)
TAVNEOS			TAVNEOS® (avacopan)
TEZSPIRE			TEZSPIRE® (tezepelumab-ekko)
Vectibix			Vectibix® (panitumumab)
XGEVA			XGEVA® (denosumab)


		Year ended December 31, 2020		Change		Year ended December 31, 2019			Year ended December 31, 2022		Change		Year ended December 31, 2021
Product sales:	Product sales:							Product sales:
U.S.	U.S.	$	17,985	9	%	$	16,531	U.S.	$	17,743	3	%	$	17,286
Rest-of-world (ROW)		6,255		10	%	5,673
ROW								ROW	7,058		1	%	7,011
Total product sales	Total product sales	24,240		9	%	22,204		Total product sales	24,801		2	%	24,297
Other revenues	Other revenues	1,184		2	%	1,158		Other revenues	1,522		(10)	%	1,682
Total revenues	Total revenues	$	25,424	9	%	$	23,362	Total revenues	$	26,323	1	%	$	25,979
Operating expenses	Operating expenses	$	16,285	19	%	$	13,688	Operating expenses	$	16,757	(9)	%	$	18,340
Operating income	Operating income	$	9,139	(6)	%	$	9,674	Operating income	$	9,566	25	%	$	7,639
Net income	Net income	$	7,264	(7)	%	$	7,842	Net income	$	6,552	11	%	$	5,893
Diluted EPS	Diluted EPS	$	12.31	(4)	%	$	12.88	Diluted EPS	$	12.11	18	%	$	10.28
Diluted shares	Diluted shares	590		(3)	%	609		Diluted shares	541		(6)	%	573


Category						Description
Research and early pipeline						R&D expenses incurred in activities substantially in support of early research through the completion of phase 1 clinical trials, including drug discovery, toxicology, pharmacokinetics and drug metabolism and process development
Later-stage clinical programs						R&D expenses incurred in or related to phase 2 and phase 3 clinical programs intended to result in registration of a new product or a new indication for an existing product primarily in the United States or the EU
Marketed products						R&D expenses incurred in support of the Company’s marketed products that are authorized to be sold primarily in the United States or the EU. Includes clinical trials designed to gather information on product safety (certain of which may be required by regulatory authorities) and their product characteristics after regulatory approval has been obtained, as well as the costs of obtaining regulatory approval of a product in a new market after approval in either the United States or the EU has been obtained


		December 31,					December 31,
		2020		2019			2022		2021
Cash, cash equivalents and marketable securities	Cash, cash equivalents and marketable securities	$	10,647	$	8,911	Cash, cash equivalents and marketable securities	$	9,305	$	8,037
Total assets	Total assets	$	62,948	$	59,707	Total assets	$	65,121	$	61,165
Current portion of long-term debt	Current portion of long-term debt	$	91	$	2,953	Current portion of long-term debt	$	1,591	$	87
Long-term debt	Long-term debt	$	32,895	$	26,950	Long-term debt	$	37,354	$	33,222
Stockholders’ equity	Stockholders’ equity	$	9,409	$	9,673	Stockholders’ equity	$	3,661	$	6,700


	Payments due by period as of December 31, 2020
Contractual obligations	Total		Year 1		Years 2 and 3		Years 4 and 5		Years 6 and beyond
Long-term debt obligations(1)(2)	$	54,293	$	1,207	$	7,857	$	4,944	$	40,285
Operating lease obligations(3)	864		166		268		102		328
Purchase obligations(4)	2,697		2,129		375		121		72
U.S. repatriation tax(5)	5,575		587		1,687		3,301		—
Unrecognized tax benefits (UTBs)(6)	—		—		—		—		—
Total contractual obligations	$	63,429	$	4,089	$	10,187	$	8,468	$	40,685


	Rebates		Chargebacks		Other deductions		Total
Balance as of December 31, 2017	$	1,867	$	272	$	108	$	2,247
Amounts charged against product sales	6,180		6,926		1,180		14,286
Payments	(5,458)		(6,744)		(1,161)		(13,363)
Balance as of December 31, 2018	2,589		454		127		3,170
Amounts charged against product sales	6,825		7,090		1,292		15,207
Payments	(6,249)		(6,985)		(1,263)		(14,497)
Balance as of December 31, 2019	3,165		559		156		3,880
Amounts charged against product sales	9,167		8,223		1,818		19,208
Payments	(8,353)		(8,191)		(1,735)		(18,279)
Balance as of December 31, 2020	$	3,979	$	591	$	239	$	4,809


		(a)	(b)		(c)		(a)	(b)		(c)
Plan category	Plan category	Number of securities to be issued upon exercise of outstanding options and rights	Weighted-average exercise price of outstanding options and rights		Number of securities remaining available for future issuance under equity compensation plans (excluding securities reflected in column (a))	Plan category	Number of securities to be issued upon exercise of outstanding options and rights	Weighted-average exercise price of outstanding options and rights		Number of securities remaining available for future issuance under equity compensation plans (excluding securities reflected in column (a))
Equity compensation plans approved by Amgen security holders:	Equity compensation plans approved by Amgen security holders:					Equity compensation plans approved by Amgen security holders:
Amended and Restated 2009 Equity Incentive Plan(1)	Amended and Restated 2009 Equity Incentive Plan(1)	9,890,702	$	179.92	23,108,576	Amended and Restated 2009 Equity Incentive Plan(1)	10,235,620	$	207.29	15,255,297
Amended and Restated 1991 Equity Incentive Plan(2)	Amended and Restated 1991 Equity Incentive Plan(2)	5,913	—		—	Amended and Restated 1991 Equity Incentive Plan(2)	2,191
Amended and Restated Employee Stock Purchase Plan	Amended and Restated Employee Stock Purchase Plan	—	—		4,393,614	Amended and Restated Employee Stock Purchase Plan				4,180,287
Total approved plans	Total approved plans	9,896,615	179.92		27,502,190	Total approved plans	10,237,811	207.29		19,435,584
Equity compensation plan not approved by Amgen security holders:	Equity compensation plan not approved by Amgen security holders:					Equity compensation plan not approved by Amgen security holders:
Amgen Profit Sharing Plan for Employees in Ireland(3)	Amgen Profit Sharing Plan for Employees in Ireland(3)	—	—		60,059	Amgen Profit Sharing Plan for Employees in Ireland(3)				222,310
Total unapproved plans	Total unapproved plans	—	—		60,059	Total unapproved plans	—	—		222,310
Total all plans	Total all plans	9,896,615	$	179.92	27,562,249	Total all plans	10,237,811	$	207.29	19,657,894


			Page number
Report of Independent Registered Public Accounting Firm (PCAOB ID: 42)			F-1

Consolidated Statements of Income for each of the three years in the period ended December 31, ~~2020~~2022			F-4

Consolidated Statements of Comprehensive Income for each of the three years in the period ended December 31, ~~2020~~2022			F-5

Consolidated Balance Sheets as of December 31, ~~2020~~2022 and ~~2019~~2021			F-6

Consolidated Statements of Stockholders’ Equity for each of the three years in the period ended December 31, ~~2020~~2022			F-7

Consolidated Statements of Cash Flows for each of the three years in the period ended December 31, ~~2020~~2022			F-8

Notes to Consolidated Financial Statements			F-9


			Page number
Schedule II. Valuation and Qualifying Accounts			F-60F-55


Exhibit No.						Description
2.1						Asset Purchase Agreement, dated August 25, 2019, by and between Amgen Inc. and Celgene Corporation. (Filed as an exhibit to Form 8-K on August 26, 2019 and incorporated herein by reference.)

~~2.2~~2.1.1						Amendment No. 1 to the Asset Purchase Agreement, dated October 17, 2019, by and between Amgen Inc. and Celgene Corporation. (Filed as an exhibit to Form 8-K on October 17, 2019 and incorporated herein by reference.)

~~2.3~~2.1.2						Amendment No. 2 to the Asset Purchase Agreement, dated October 17, 2019, by and between Amgen Inc. and Celgene Corporation. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~2.4~~2.2						Letter Agreement, dated November 21, 2019, by and between Amgen Inc. and the parties named therein re: Treatment of Certain Product Inventory in connection with Amgen’s acquisition of ~~Otezla®~~Otezla (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~2.5~~2.3						Irrevocable Guarantee, dated August 25, 2019, by and between Amgen Inc. and Bristol-Myers Squibb Company. (Filed as an exhibit to Form 8-K on August 26, 2019 and incorporated herein by reference.)

2.4						Agreement and Plan of Merger, dated July 27, 2021, by and among Amgen Inc., Teneobio, Inc., Tuxedo Merger Sub, Inc., and Fortis Advisors LLC. (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential)(Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2021 on November 3, 2021 and incorporated herein by reference.)


Exhibit No.						Description
2.5						Agreement and Plan of Merger, dated as of August 3, 2022, among ChemoCentryx, Inc., Amgen Inc. and Carnation Merger Sub, Inc. (Filed as an exhibit to Form 8-K on August 4, 2022 and incorporated herein by reference.)

2.6						Transaction Agreement, dated as of December 11, 2022, by and among Amgen Inc., Pillartree Limited and Horizon Therapeutics plc. (Filed as an exhibit to Form 8-K on December 12, 2022 and incorporated herein by reference.)

2.7						Appendix 3 to the Rule 2.7 Announcement, dated as of December 12, 2022 (Conditions Appendix). (Filed as an exhibit to Form 8-K on December 12, 2022 and incorporated herein by reference.)

3.1						Restated Certificate of Incorporation of Amgen Inc. (As Restated March 6, 2013.) (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2013 on May 3, 2013 and incorporated herein by reference.)

3.2						Amended and Restated Bylaws of Amgen Inc. (As Amended and Restated February 15, 2016.) (Filed as an exhibit to Form 8-K on February 17, 2016 and incorporated herein by reference.)


4.1						Form of stock certificate for the common stock, par value $.0001 of the Company. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 1997 on May 14, 1997 and incorporated herein by reference.)

4.2						Form of Indenture, dated January 1, 1992. (Filed as an exhibit to Form S-3 Registration Statement filed on December 19, 1991 and incorporated herein by reference.)

4.3						Agreement of Resignation, Appointment and Acceptance dated February 15, 2008. (Filed as an exhibit to Form 10-K for the year ended December 31, 2007 on February 28, 2008 and incorporated herein by reference.)

4.4						First Supplemental Indenture, dated February 26, 1997. (Filed as an exhibit to Form 8-K on March 14, 1997 and incorporated herein by reference.)

4.5						8-1/8% Debentures due April 1, 2097. (Filed as an exhibit to Form 8-K on April 8, 1997 and incorporated herein by reference.)

4.6						Officer’s Certificate of Amgen Inc., dated April 8, 1997, establishing a series of securities entitled “8 1/8% Debentures due April 1, 2097.” (Filed as an exhibit to Form 8-K on April 8, 1997 and incorporated herein by reference.)

4.7						Indenture, dated August 4, 2003. (Filed as an exhibit to Form S-3 Registration Statement on August 4, 2003 and incorporated herein by reference.)

4.8						Corporate Commercial Paper - Master Note between and among Amgen Inc., as Issuer, Cede & Co., as Nominee of The Depository Trust Company, and Citibank, N.A., as Paying Agent. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 1998 on May 13, 1998 and incorporated herein by reference.)

4.9						Officers’ Certificate of Amgen Inc., dated May 30, 2007, including form of the Company’s 6.375% Senior Notes due 2037. (Filed as an exhibit to Form 8-K on May 30, 2007 and incorporated herein by reference.)

4.10						Officers’ Certificate of Amgen Inc., dated May 23, 2008, including form of the Company’s 6.90% Senior Notes due 2038. (Filed as exhibit to Form 8-K on May 23, 2008 and incorporated herein by reference.)

4.11						Officers’ Certificate of Amgen Inc., dated January 16, 2009, including form of the Company’s 6.40% Senior Notes due 2039. (Filed as exhibit to Form 8-K on January 16, 2009 and incorporated herein by reference.)

4.12						Officers’ Certificate of Amgen Inc., dated March 12, 2010, including form of the Company’s 5.75% Senior Notes due 2040. (Filed as exhibit to Form 8-K on March 12, 2010 and incorporated herein by reference.)

4.13						Officers’ Certificate of Amgen Inc., dated September 16, 2010, including form of the Company’s 4.95% Senior Notes due 2041. (Filed as an exhibit to Form 8-K on September 17, 2010 and incorporated herein by reference.)

4.14						Officers’ Certificate of Amgen Inc., dated June 30, 2011, including form of the Company’s 5.65% Senior Notes due 2042. (Filed as an exhibit to Form 8-K on June 30, 2011 and incorporated herein by reference.)

4.15						Officers’ Certificate of Amgen Inc., dated November 10, 2011, including form of the Company’s 5.15% Senior Notes due 2041. (Filed as an exhibit to Form 8-K on November 10, 2011 and incorporated herein by reference.)


Exhibit No.						Description
4.16						Officers’ Certificate of Amgen Inc., dated December 5, 2011, including form of the Company’s 5.50% Senior Notes due 2026. (Filed as an exhibit to Form 8-K on December 5, 2011 and incorporated herein by reference.)

4.17						Officers’ Certificate of Amgen Inc., dated May 15, 2012, including ~~forms~~form of the Company’s ~~3.625% Senior Notes due 2022 and~~ 5.375% Senior Notes due 2043. (Filed as an exhibit to Form 8-K on May 15, 2012 and incorporated herein by reference.)

4.18						Officers’ Certificate of Amgen Inc., dated September 13, 2012, including form of the Company’s 4.000% Senior Notes due 2029. (Filed as an exhibit to Form 8-K on September 13, 2012 and incorporated herein by reference.)

4.19						Indenture, dated May 22, 2014, between Amgen Inc. and The Bank of New York Mellon Trust Company, N.A., as Trustee. (Filed as an exhibit to Form 8-K on May 22, 2014 and incorporated herein by reference.)

4.20						Officers’ Certificate of Amgen Inc., dated May 22, 2014, including form of the Company’s 3.625% Senior Notes due 2024. (Filed as an exhibit to Form 8-K on May 22, 2014 and incorporated herein by reference.)


4.21						Officer’s Certificate of Amgen Inc., dated May 1, 2015, including forms of the Company’s ~~2.700% Senior Notes due 2022,~~ 3.125% Senior Notes due 2025 and 4.400% Senior Notes due 2045. (Filed as an exhibit on Form 8-K on May 1, 2015 and incorporated herein by reference.)

4.22						Officer’s Certificate of Amgen Inc., dated as of February 25, 2016, including ~~forms~~form of the Company’s ~~1.250% Senior Notes due 2022 and~~ 2.000% Senior Notes due 2026. (Filed as an exhibit on Form 8-K on February 26, 2016 and incorporated herein by reference.)

4.23						Form of Permanent Global Certificate for the Company’s 0.410% bonds due 2023. (Filed as an exhibit on Form 8-K on March 8, 2016 and incorporated herein by reference.)

4.24						Terms of the Bonds for the Company’s 0.410% bonds due 2023. (Filed as an exhibit on Form 8-K on March 8, 2016 and incorporated herein by reference.)

4.25						Officer’s Certificate of Amgen Inc., dated as of June 14, 2016, including forms of the Company’s 4.563% Senior Notes due 2048 and 4.663% Senior Notes due 2051. (Filed as an exhibit to Form 8-K on June 14, 2016 and incorporated herein by reference.)

4.26						Officer’s Certificate of Amgen Inc., dated as of August 19, 2016, including forms of the Company’s 2.250% Senior Notes due 2023 and 2.600% Senior Notes due 2026. (Filed as an exhibit to Form 8-K on August 19, 2016 and incorporated herein by reference.)

4.27						Officer’s Certificate of Amgen Inc., dated as of ~~May 11, 2017 including form~~ ~~of the Company’s~~ ~~2.650% Senior Notes due 2022.~~ ~~(Filed as an exhibit to Form 8-K on May 11, 2017 and incorporated herein by reference.)~~

~~4.28~~						~~Officer’s Certificate of Amgen Inc., dated as of~~ November 2, 2017, including in the form of the Company’s 3.200% Senior Notes due 2027. (Filed as an exhibit to Form 8-K on November 2, 2017 and incorporated herein by reference.)

~~4.29~~4.28						Officer’s Certificate of Amgen Inc., dated as of February 21, 2020, including forms of the Company’s 1.900% Senior Notes due 2025, 2.200% Senior Notes due 2027, 2.450% Senior Notes due 2030, 3.150% Senior Notes due 2040 and 3.375% Senior Notes due 2050. (Filed as an exhibit to Form 8-K on February 21, 2020 and incorporated herein by reference.)

~~4.30~~4.29						Officer’s Certificate of Amgen Inc., dated as of May 6, 2020, including form of the Company’s 2.300% Senior Notes due 2031. (Filed as an exhibit to Form 8-K on May 6, 2020 and incorporated herein by reference.)

~~4.31~~4.30						Officer’s Certificate of Amgen Inc., dated as of August 17, 2020, including forms of the Company’s 2.770% Senior Notes due 2053. (Filed as an exhibit to Form 8-K on August 18, 2020 and incorporated herein by reference.)

~~4.32~~4.31						~~Registration Rights Agreement,~~Officer’s Certificate of Amgen Inc., dated as of August ~~17, 2020, by~~9, 2021, including forms of the Company’s 1.650% Senior Notes due 2028, 2.000% Senior Notes due 2032, 2.800% Senior Notes due 2041 and among Amgen Inc., BofA Securities, Inc. and J.P. Morgan Securities LLC, as lead dealer managers, and BNP Paribas Securities Corp., Deutsche Bank Securities Inc., RBC Capital Markets, LLC, Blaylock Van, LLC and Siebert Williams Shank & Co., LLC, as co-dealer managers 3.000% Senior Notes due 2052.~~(Filed~~ (Filed as an exhibit to Form 8-K on August ~~18, 2020~~9, 2021 and incorporated herein by reference.)

4.33*4.32						Officer’s Certificate of Amgen Inc., dated as of February 22, 2022, including forms of the Company’s 3.000% Senior Notes due 2029, 3.350% Senior Notes due 2032, 4.200% Senior Notes due 2052 and 4.400% Senior Notes due 2062. (Filed as an exhibit to Form 8-K on February 22, 2022 and incorporated herein by reference.)

4.33						Officer’s Certificate of Amgen Inc., dated as of August 18, 2022, including forms of the Company’s 4.050% Senior Notes due 2029, 4.200% Senior Notes due 2033 and 4.875% Senior Notes due 2053. (Filed as an exhibit to Form 8-K on August 18, 2022 and incorporated herein by reference.)


Exhibit No.						Description

4.34*						Description of Amgen Inc.’s Securities Registered Pursuant to Section 12 of the Securities Exchange Act of 1934.

10.1+						Amgen Inc. Amended and Restated 2009 Equity Incentive Plan. (Filed as Appendix C to the Definitive Proxy Statement on Schedule 14A on April 8, 2013 and incorporated herein by reference.)

10.2+						First Amendment to Amgen Inc. Amended and Restated 2009 Equity Incentive Plan, effective March 4, 2015. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2015 on April 27, 2015 and incorporated herein by reference.)

10.3+						Second Amendment to Amgen Inc. Amended and Restated 2009 Equity Incentive Plan, effective March 2, 2016. (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2016 on May 2, 2016 and incorporated herein by reference.)

10.4+*						Form of Grant of Stock Option Agreement for the Amgen Inc. Amended and Restated 2009 Equity Incentive Plan. (As Amended and Restated on December 15 ~~, 20~~20 .12, 2022.)

10.5+*						Form of Restricted Stock Unit Agreement for the Amgen Inc. Amended and Restated 2009 Equity Incentive Plan. (As Amended and Restated on December ~~15,2020.~~12, 2022.)


~~10.19+~~Exhibit No.						Description
10.14+						Amgen Nonqualified Deferred Compensation Plan. (As Amended and Restated effective October 16, 2013.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2013 on February 24, 2014 and incorporated herein by reference.)

~~10.20+~~10.14.1+						First Amendment to the Amgen Nonqualified Deferred Compensation Plan, effective October 14, 2016. (Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2016 on October 28, 2016 and incorporated herein by reference.)

~~10.21+~~10.14.2+						Second Amendment to the Amgen Nonqualified Deferred Compensation Plan, ~~(As Amended and Restated~~ effective January 1, ~~2020).~~2020. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)


~~10.22+~~10.14.3+						~~Agreement between~~Third Amendment to the Amgen ~~Inc. and Murdo Gordon, dated July 25, 2018.~~Nonqualified Deferred Compensation Plan, effective January 1, 2022. (Filed as an exhibit to Form ~~10-Q~~10-K for the ~~quarter~~year ended ~~September 30, 2018~~December 31, 2021 on ~~October 31, 2018~~February 16, 2022 and incorporated herein by reference.)

~~10.23+~~10.15+						Aircraft Time Sharing Agreement, dated December 3, 2021, by and between Amgen Inc. and ~~Peter Griffith, dated October 18, 2019.~~Robert A. Bradway. (Filed as an exhibit to Form ~~10-Q~~10-K for the ~~quarter~~year ended ~~March~~December 31, ~~2020~~2021 on ~~May 1, 2020~~February 16, 2022 and incorporated herein by reference.)


~~10.24~~10.16						Second Amended and Restated Credit Agreement, dated December 12, 2019, among Amgen Inc., the Banks therein named, Citibank, N.A., as administrative agent, and JPMorgan Chase Bank, N.A., as syndication agent. (Filed as an exhibit to Form 8-K on December 12, 2019 and incorporated herein by reference.)

~~10.25~~10.16.1*						Amendment No. 1 to the Second Amended and Restated Credit Agreement, dated as of December 29, 2022, between Amgen Inc. and Citibank, N.A., as the Administrative Agent and an Issuing Bank.

10.17						Bridge Credit Agreement, dated as of December 12, 2022, by and among Amgen Inc., Citibank, N.A., as administrative agent, Bank of America, N.A., as syndication agent, Citibank, N.A. and Bank of America, N.A., as lead arrangers and book runners, and the other banks party thereto. (Filed as an exhibit to Form 8-K on December 12, 2022 and incorporated herein by reference.)

10.18						Term Loan Credit Agreement, dated as of December 22, 2022, by and among Amgen Inc., Citibank, N.A., as administrative agent, Bank of America, N.A., as syndication agent, Citibank, N.A., Bank of America, N.A., Goldman Sachs Bank USA and Mizuho Bank, Ltd., as lead arrangers and book runners, Goldman Sachs Bank USA and Mizuho Bank, Ltd. as documentation agents, and the other banks party thereto. (Filed as an exhibit to Form 8-K on December 22, 2022 and incorporated herein by reference.)

10.19						Collaboration and License Agreement between Amgen Inc. and Celltech R&D Limited dated May 10, 2002 (portions of the exhibit have been omitted pursuant to a request for confidential treatment) and Amendment No. 1, effective June 9, 2003, to Collaboration and License Agreement between Amgen Inc. and Celltech R&D Limited (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-K/A for the year ended December 31, 2012 on July 31, 2013 and incorporated herein by reference.)

~~10.26~~10.19.1						Amendment No. 2 to Collaboration and License Agreement, effective November 14, 2016, between Amgen Inc. and Celltech R&D Limited (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-K for the year ended December 31, 2016 on February 14, 2017 and incorporated herein by reference.)

~~10.27~~10.20						Letter Agreement, dated June 25, 2019, by and between Amgen Inc. and UCB Celltech (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2019 on July 31, 2019 and incorporated herein by reference.)

~~10.28~~						~~Collaboration Agreement, dated April 22, 1994, by and between Bayer Corporation (formerly Miles, Inc.) and Onyx Pharmaceuticals, Inc.~~ ~~(Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2011 by Onyx Pharmaceuticals, Inc. on May 10, 2011 and incorporated herein by reference.)~~

~~10.29~~						~~Amendment to Collaboration Agreement, dated April 24, 1996, by and between Bayer Corporation and Onyx Pharmaceuticals, Inc.~~ ~~(Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2006 by Onyx Pharmaceuticals, Inc. on May 10, 2006 and incorporated herein by reference.)~~

~~10.30~~						~~Amendment to Collaboration Agreement, dated February 1, 1999, by and between Bayer Corporation and Onyx Pharmaceuticals, Inc.~~ ~~(Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2006 by Onyx Pharmaceuticals, Inc. on May 10, 2006 and incorporated herein by reference.)~~

~~10.31~~						~~Settlement Agreement and Release, dated October 11, 2011, by and between Bayer Corporation, Bayer AG, Bayer HealthCare LLC and Bayer Pharma AG and Onyx Pharmaceuticals, Inc.~~ ~~(Filed as an exhibit to Form 10-K for the year ended December 31, 2011 by Onyx Pharmaceuticals, Inc. on February 27, 2012 and incorporated herein by reference.)~~

~~10.32~~						~~Fourth Amendment to Collaboration Agreement, dated October 11, 2011, by and between Bayer Corporation and Onyx Pharmaceuticals, Inc.~~ ~~(Filed as an exhibit to Form 10-K for the year ended December 31, 2011 by Onyx Pharmaceuticals, Inc. on February 27, 2012 and incorporated herein by reference.)~~

~~10.33~~						~~Side Letter Regarding Collaboration Agreement, dated May 29, 2015, by and between Bayer HealthCare LLC and Onyx Pharmaceuticals, Inc.~~ ~~(Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2015 on August 5, 2015 and incorporated herein by reference.)~~

~~10.34~~						~~Side Letter Regarding Collaboration Agreement and Stivarga Agreement, dated February 13, 2020, by and between Onyx Pharmaceuticals, Inc. and Bayer HealthCare LLC.~~ ~~(Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2020 on May 1, 2020 and incorporated herein by reference.)~~

~~10.35~~						~~Sourcing and Supply Agreement, dated January 6, 2017, by and between Amgen USA Inc., a wholly owned subsidiary of Amgen Inc., and DaVita Inc~~. (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2017 on April 27, 2017 and incorporated herein by reference.)

~~10.36~~						~~Exclusive License and Collaboration Agreement, dated August 28, 2015, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2017 on July 26, 2017 and incorporated herein by reference.)

~~10.37~~						~~Amendment No. 1 to the Exclusive License and Collaboration Agreement, dated April 21, 2017, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2017 on July 26, 2017 and incorporated herein by reference.)

~~10.38~~						~~Amendment No. 2 to the Exclusive License and Collaboration Agreement, dated April 21, 2017, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2017 on July 26, 2017 and incorporated herein by reference.)


~~10.39~~						~~Collaboration Agreement, dated April 21, 2017, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2017 on July 26, 2017 and incorporated herein by reference.)
~~10.40~~						~~Amendment No. 1 to the Collaboration Agreement, dated March 20, 2018, by and between Novartis Pharma AG and Amgen Inc~~. (portions of the exhibit have been omitted pursuant to a request for confidential treatment). (Filed as an exhibit to Form 10-Q for the quarter ended March 31, 2018 on April 25, 2018 and incorporated herein by reference.)

~~10.41~~						~~Amendment No. 2 to the Collaboration Agreement, dated August 19, 2020, by and between Amgen Inc. and Novartis Pharma AG~~ (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.) (Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2020 on October 29, 2020 and incorporated herein by reference.)

~~10.42~~10.21						Collaboration Agreement, dated October 31, 2019, by and between Amgen Inc. and BeiGene Switzerland GmbH, a wholly-owned subsidiary of BeiGene, Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed). (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~10.43~~10.21.1						First Amendment to Collaboration Agreement, dated April 20, 2022, by and between Amgen Inc. and BeiGene Switzerland GmbH, and BeiGene, Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2022 on August 5, 2022 and incorporated herein by reference.)


Exhibit No.						Description
10.22						Guarantee, dated as of October 31, 2019, made by and among BeiGene, Ltd. and Amgen Inc. (Filed as an exhibit to Form 10-K for the year ended December 31, 2019 on February 12, 2020 and incorporated herein by reference.)

~~10.44~~10.23						Share Purchase Agreement, dated October 31, 2019, by and between Amgen Inc. and BeiGene, Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed). (Filed as an exhibit to Schedule 13D on January 8, 2020 and incorporated herein by reference.)

~~10.45~~10.23.1						Amendment No. 1 to Share Purchase Agreement, dated December 6, 2019, by and among BeiGene, Ltd. and Amgen Inc. (Filed as an exhibit to Schedule 13D on January 8, 2020 and incorporated herein by reference.)

~~10.46~~10.23.2						Restated Amendment No. 2 to Share Purchase Agreement, dated September 24, 2020, by and among BeiGene, Ltd. and Amgen Inc. (Filed as an exhibit to Form 10-Q for the quarter ended September 30, 2020 on October 29, 2020 and incorporated herein by reference.)

~~10.47~~10.24						Collaboration Agreement dated March 30, 2012 by and between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC, a wholly owned subsidiary of AstraZeneca Pharmaceuticals LP~~(portions~~ (portions of the exhibit have been omitted ~~pursuant to a request for confidential treatment).~~because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form 10-Q for the quarter ended ~~March 31, 2012~~June 30, 2022 on ~~May 8, 2012~~August 5, 2022 and incorporated herein by reference.)

~~10.48~~10.24.1						Amendment No. 1 to the Collaboration Agreement, dated October 1, 2014, by and among Amgen Inc., AstraZeneca Collaboration Ventures, LLC and AstraZeneca Pharmaceuticals LP~~(portions~~ (portions of the exhibit have been omitted ~~pursuant to a request for confidential treatment).~~because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form ~~10-K~~10-Q for the ~~year~~quarter ended ~~December 31, 2014~~June 30, 2022 on ~~February 19, 2015~~August 5, 2022 and incorporated herein by reference.)

~~10.49~~10.24.2						Amendment Nos. 2 through 6 to the March 30, 2012 Collaboration Agreement between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC, dated May 2 and 27 and October 2, 2016, January 31, 2018, and May 15, 2020, respectively (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.) (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2020 on July 29, 2020 and incorporated herein by reference.)

10.50*10.24.3						Amendment No. 7 to the Collaboration Agreement, dated December ~~18,~~17, 2020, by and between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2020 on February 9, 2021 and incorporated herein by reference.)

10.24.4						Amendment No. 8 to the Collaboration Agreement, dated November 19, 2021, by and between Amgen Inc. and AstraZeneca Collaboration Ventures, LLC (portions of the exhibit have been omitted because they are both (i) not material and (ii) is the type of information that the Company treats as private or confidential.) (Filed as an exhibit to Form 10-K for the year ended December 31, 2021 on February 16, 2022 and incorporated herein by reference.)

10.25						License and Collaboration Agreement, dated June 1, 2021, by and between Amgen Inc. and Kyowa Kirin Co., Ltd. (portions of the exhibit have been omitted because they are both (i) not material and (ii) would be competitively harmful if publicly disclosed). (Filed as an exhibit to Form 10-Q for the quarter ended June 30, 2021 on August 4, 2021 and incorporated herein by reference.)

21*						Subsidiaries of the Company.

23						Consent of the Independent Registered Public Accounting Firm. The consent is set forth on page 9491 of this Annual Report on the 10-K.

24						Power of Attorney. The Power of Attorney is set forth on page 9592 of this Annual Report on Form 10-K.

31*						Rule 13a-14(a) Certifications.

32**						Section 1350 Certifications.


101.INS						Inline XBRL Instance Document - ~~the~~The instance document does not appear in the interactive data file because its XBRL tags are embedded within the Inline XBRL document.

101.SCH*						Inline XBRL Taxonomy Extension Schema Document.


Exhibit No.						Description
101.CAL*						Inline XBRL Taxonomy Extension Calculation Linkbase Document.

101.DEF*						Inline XBRL Taxonomy Extension Definition Linkbase Document.

101.LAB*						Inline XBRL Taxonomy Extension Label Linkbase Document.

101.PRE*						Inline XBRL Taxonomy Extension Presentation Linkbase Document.

104						Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101).


						Sales deductions
Description of the Matter						As of December 31, ~~2020,~~2022, the Company recorded accrued sales deductions of ~~$4.8~~$6.0 billion. As described in Note 1 to the financial statements under the caption “Product sales and sales deductions,” revenues from product sales are recognized net of accruals for estimated rebates, wholesaler chargebacks, discounts and other deductions (collectively sales deductions), which are established at the time of sale. Auditing the estimation of sales deductions, which are netted against product sales, is complex, requires significant judgment, and the amounts involved are material to the financial statements taken as a whole.Revenue from product sales is recognized upon transfer of control of a product to a customer, generally upon delivery, and is based on an amount that reflects the consideration to which the Company expects to be entitled, which represents an amount that is net of accruals for estimated sales deductions. The estimated sales deductions are based on current contractual and statutory requirements, market events and trends, internal and external historical data, and forecasted customer buying patterns.

How We Addressed the Matter in Our Audit						We obtained an understanding, evaluated the design and tested the operating effectiveness of internal controls over the sales deduction processes. This included testing controls over management’s review of significant assumptions and inputs used in the estimate of sales deductions, including actual sales, contractual terms, historical experience, wholesaler inventory levels, demand data and estimated patient population. We also tested management’s controls over the accuracy of forecasting demand activity as well as the completeness and accuracy of the significant components included in the final sales deduction estimates. To test management’s estimated sales deductions, we obtained management’s calculations for the respective estimates and performed the following procedures, among others. We tested management’s estimation process over the determination of sales discount accruals by developing an independent expectation of the estimated accrual balances, including comparing accrual balances recorded by management to those implied by historical payment trends, performing a lookback analysis using actual historical data to evaluate the forecasted amounts, assessing subsequent events to determine whether there was any new information that would require adjustment to the initial accruals, evaluating trends in actual sales and discount accrual balances, comparing cash receipts to product sales, confirming terms and conditions for a sample of contracts, ~~with the Company’s customers,~~ testing a sample of credits issued and payments made throughout the year, and agreeing rates to underlying contract terms.


						Unrecognized tax benefits
Description of the Matter						As discussed in Notes 1 and 6 to the consolidated financial statements, the Company operates in various jurisdictions in which differing interpretations of complex tax laws and regulations create uncertainty and necessitate the use of significant judgment in the determination of the Company’s unrecognized tax benefits related to allocation of profits among various jurisdictions (“transfer pricing”), particularly in the U.S. federal tax jurisdiction where the Company has significant assets and operations. In this regard, the Company uses significant judgment in (1) determining whether a tax position’s technical merits are more-likely-than-not to be sustained and (2) measuring the amount of tax benefit that qualifies for recognition. As of December 31, ~~2020,~~2022, the Company accrued ~~$3.4~~$3.8 billion of gross unrecognized tax benefits including those related to transfer pricing. Auditing the assessment of the technical merits and measurement of the Company’s unrecognized tax benefits is challenging ~~because they~~and can be complex, highly judgmental, and based on interpretations of tax laws and regulations and application of those interpretations to the Company’s facts and circumstances.

How We Addressed the Matter in Our Audit						We obtained an understanding, evaluated the design and tested the operating effectiveness of internal controls over the Company’s process to assess the technical merits of its tax positions, as well as management’s process to measure the unrecognized tax benefits of those tax positions, particularly in regard to transfer pricing. This included testing controls over management’s review of the inputs, calculations, assumptions and methods selected to measure the amount of tax benefits that qualify for recognition. We involved tax and transfer pricing ~~professionals~~specialists to assist in assessing the technical merits and measurement of certain of the Company’s unrecognized tax benefits. Depending on the nature of the specific tax position and, as applicable, developments with the relevant tax authorities, our procedures included obtaining and reviewing the Company’s correspondence with such tax authorities and evaluating certain third-party advice to support the Company’s evaluations and recorded positions. We used our knowledge of and experience with how the income tax laws and regulations related to transfer pricing are applied by the relevant tax authorities to evaluate the Company’s accounting for its unrecognized tax benefits. We evaluated developments in the applicable regulatory environments to assess potential effects on the Company’s recorded positions. We assessed management’s consideration of current tax controversy, litigation and tax litigation trends. We analyzed the assumptions and data used by the Company when it determined the amount of tax benefits to recognize, including applicable interest and penalties, and we tested the accuracy of those underlying calculations. We have also evaluated the Company’s income tax disclosures included in Note 6 in relation to these matters.

						/s/ Ernst & Young LLP


		Number of shares of common stock	Common stock and additional paid-in capital		Accumulated deficit		Accumulated other comprehensive (loss) income		Total			Number of shares of common stock	Common stock and additional paid-in capital		Accumulated deficit		Accumulated other comprehensive (loss) income		Total
Balance as of December 31, 2017		722.2	$	30,992	$	(5,072)	$	(679)	$	25,241
Cumulative effect of changes in accounting principles, net of taxes		—	—		38		(9)		29
Net income		—	—		8,394		—		8,394
Other comprehensive loss, net of taxes		—	—		—		(81)		(81)
Dividends declared on common stock ($5.41 per share)		—	—		(3,482)		—		(3,482)
Issuance of common stock in connection with the Company’s equity award programs		1.9	56		—		—		56
Stock-based compensation expense		—	327		—		—		327
Tax impact related to employee stock-based compensation expense		—	(129)		—		—		(129)
Repurchases of common stock		(94.5)	—		(17,855)		—		(17,855)
Balance as of December 31, 2018		629.6	31,246		(17,977)		(769)		12,500

Net income		—	—		7,842		—		7,842
Other comprehensive income, net of taxes		—	—		—		241		241
Dividends declared on common stock ($5.95 per share)		—	—		(3,555)		—		(3,555)
Issuance of common stock in connection with the Company’s equity award programs		2.0	97		—		—		97
Stock-based compensation expense		—	323		—		—		323
Tax impact related to employee stock-based compensation expense		—	(135)		—		—		(135)
Repurchases of common stock		(40.2)	—		(7,640)		—		(7,640)
Balance as of December 31, 2019	Balance as of December 31, 2019	591.4	31,531		(21,330)		(528)		9,673		Balance as of December 31, 2019	591.4	$	31,531	$	(21,330)	$	(528)	$	9,673
Cumulative effect of changes in accounting principles, net of taxes	Cumulative effect of changes in accounting principles, net of taxes	—	—		(2)		—		(2)		Cumulative effect of changes in accounting principles, net of taxes	—	—		(2)		—		(2)
Net income	Net income	—	—		7,264		—		7,264		Net income	—	—		7,264		—		7,264
Other comprehensive loss, net of taxes	Other comprehensive loss, net of taxes	—	—		—		(457)		(457)		Other comprehensive loss, net of taxes	—	—		—		(457)		(457)
Dividends declared on common stock ($6.56 per share)	Dividends declared on common stock ($6.56 per share)	—	—		(3,843)		—		(3,843)		Dividends declared on common stock ($6.56 per share)	—	—		(3,843)		—		(3,843)
Issuance of common stock in connection with the Company’s equity award programs	Issuance of common stock in connection with the Company’s equity award programs	2.1	91		—		—		91		Issuance of common stock in connection with the Company’s equity award programs	2.1	91		—		—		91
Stock-based compensation expense	Stock-based compensation expense	—	349		—		—		349		Stock-based compensation expense	—	349		—		—		349
Tax impact related to employee stock-based compensation expense	Tax impact related to employee stock-based compensation expense	—	(169)		—		—		(169)		Tax impact related to employee stock-based compensation expense	—	(169)		—		—		(169)
Repurchases of common stock	Repurchases of common stock	(15.2)	—		(3,497)		—		(3,497)		Repurchases of common stock	(15.2)	—		(3,497)		—		(3,497)
Balance as of December 31, 2020											Balance as of December 31, 2020	578.3	31,802		(21,408)		(985)		9,409

Balance as of December 31, 2020		578.3	$	31,802	$	(21,408)	$	(985)	$	9,409
Net income											Net income	—	—		5,893		—		5,893
Other comprehensive income, net of taxes											Other comprehensive income, net of taxes	—	—		—		189		189
Dividends declared on common stock ($7.22 per share)											Dividends declared on common stock ($7.22 per share)	—	—		(4,098)		—		(4,098)
Issuance of common stock in connection with the Company’s equity award programs											Issuance of common stock in connection with the Company’s equity award programs	1.7	82		—		—		82
Stock-based compensation expense											Stock-based compensation expense	—	361		—		—		361
Tax impact related to employee stock-based compensation expense											Tax impact related to employee stock-based compensation expense	—	(149)		—		—		(149)
Repurchases of common stock											Repurchases of common stock	(21.7)	—		(4,987)		—		(4,987)
Balance as of December 31, 2021											Balance as of December 31, 2021	558.3	32,096		(24,600)		(796)		6,700

Net income											Net income	—	—		6,552		—		6,552
Other comprehensive income, net of taxes											Other comprehensive income, net of taxes	—	—		—		565		565
Dividends declared on common stock ($7.95 per share)											Dividends declared on common stock ($7.95 per share)	—	—		(4,264)		—		(4,264)
Issuance of common stock in connection with the Company’s equity award programs											Issuance of common stock in connection with the Company’s equity award programs	1.8	138		—		—		138
Stock-based compensation expense											Stock-based compensation expense	—	419		—		—		419
Tax impact related to employee stock-based compensation expense											Tax impact related to employee stock-based compensation expense	—	(139)		—		—		(139)
Repurchases of common stock											Repurchases of common stock	(26.1)	—		(6,310)		—		(6,310)

Balance as of December 31, 2022											Balance as of December 31, 2022	534.0	$	32,514	$	(28,622)	$	(231)	$	3,661


	Amounts
Cash ~~purchase price~~and cash equivalents	$	~~13,400~~86
~~Transaction costs~~Marketable securities	40235
~~Accumulated cost (consideration transferred)~~Inventories	$		~~13,440~~41

~~Intangible assets:~~
~~Developed-product-technology~~Finite-lived intangible assets – developed-product-technology rights	$		~~13,007~~3,497
~~Marketing-related rights~~Goodwill	~~195~~667
~~Inventory~~Other liabilities, net	~~367~~ (85)
Deferred tax liability, net	~~(24)~~
~~Deferred credit~~	~~(96)~~
~~Other liabilities, net~~	~~(9)~~(516)
Total assets acquired, net	$	~~13,440~~3,925


	Amounts
~~Total cash paid to Kirin~~Cash purchase price	$	~~780~~993
~~Fair value of contingent~~Contingent consideration ~~obligation~~	45
~~Loss on settlement of preexisting relationship~~	~~(168)~~299
Total consideration ~~transferred to acquire K-A~~	~~657~~$	1,292

~~Fair value of Amgen’s investment in K-A~~	~~825~~
~~Total acquisition date fair value~~Cash and cash equivalents	$	~~1,482~~100
IPR&D	991
Finite-lived intangible asset – R&D technology rights	115
Finite-lived intangible assets – licensing rights	41
Goodwill	273
Other assets, net	16
Deferred tax liability	(244)
Total assets acquired, net	$	1,292


	Year ended December 31, 2020						Year ended December 31, 2019						Year ended December 31, 2018
	U.S.		ROW		Total		U.S.		ROW		Total		U.S.		ROW		Total
Enbrel® (etanercept)	$	4,855	$	141	$	4,996	$	5,050	$	176	$	5,226	$	4,807	$	207	$	5,014
Prolia® (denosumab)	1,830		933		2,763		1,772		900		2,672		1,500		791		2,291
Neulasta® (pegfilgrastim)	2,001		292		2,293		2,814		407		3,221		3,866		609		4,475
Otezla®(1)	1,790		405		2,195		139		39		178		0		0		0
XGEVA® (denosumab)	1,405		494		1,899		1,457		478		1,935		1,338		448		1,786
Aranesp® (darbepoetin alfa)	629		939		1,568		758		971		1,729		942		935		1,877
KYPROLIS® (carfilzomib)	710		355		1,065		654		390		1,044		583		385		968
Repatha® (evolocumab)	459		428		887		376		285		661		358		192		550
Other products	4,306		2,268		6,574		3,511		2,027		5,538		4,035		1,537		5,572
Total product sales(2)	17,985		6,255		24,240		16,531		5,673		22,204		17,429		5,104		22,533
Other revenues	511		673		1,184		693		465		1,158		929		285		1,214
Total revenues	$	18,496	$	6,928	$	25,424	$	17,224	$	6,138	$	23,362	$	18,358	$	5,389	$	23,747


		Year ended December 31, 2020				Year ended December 31, 2022
		Units (in millions)	Weighted-average grant date fair value			Units (in millions)	Weighted-average grant date fair value
Balance nonvested as of December 31, 2019		3.1	$	174.97
Balance nonvested as of December 31, 2021					Balance nonvested as of December 31, 2021	3.0	$	217.95
Granted	Granted	1.1	$	235.63	Granted	1.0	$	234.47
Vested	Vested	(1.0)	$	167.23	Vested	(0.9)	$	201.47
Forfeited	Forfeited	(0.2)	$	190.15	Forfeited	(0.3)	$	226.15
Balance nonvested as of December 31, 2020		3.0	$	198.11
Balance nonvested as of December 31, 2022					Balance nonvested as of December 31, 2022	2.8	$	228.71